NCBI Conserved Domain Search

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 82.31 E-value: 1.36e-18

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATN 77

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: 79.43 E-value: 1.28e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1179 APNPLCVVPGEPVVLSCELSRASAQVFWSHNGSPVQ--QGEGLELRAegpRRILCIQAADLAHTGVYTCQSGASP-GAPS 1255
Cdd:cd04979      2 SFKQISVKEGDTVILSCSVKSNNAPVTWIHNGKKVPryRSPRLVLKT---ERGLLIRSAQEADAGVYECHSGERVlGSTL 78


                   ....*....
gi 1883538138 1256 LSFNVQVAE 1264
Cdd:cd04979     79 RSVTLHVLE 87

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: 1.12e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   134 PQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGmaLDEVWDSSHFKLepgrgaSDEGASLTLRILAARLPDSGVYVCHARN 213
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQG--GKLLAESGRFSV------SRSGSTSTLTISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 1883538138   214 AHGHAQAGALLQV 226
Cdd:smart00410   73 SSGSASSGTTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 73.45 E-value: 1.67e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHFKLepgrgaSDEGASLTLRILAARLPDSGVY 207
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS---SDRFKV------TYEGGTYTLTISNVQPDDSGKY 71

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:pfam07679   72 TCVATNSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.90 E-value: 1.78e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVwdsshfklePGRGASDEGASLTLRILAARLPDSGVY 207
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSG---------STRSRSLSGSNSTLTISNVTRSDAGTY 72


                   ....*.
gi 1883538138  208 VCHARN 213
Cdd:pfam13927   73 TCVASN 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 69.21 E-value: 4.53e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMyRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:pfam07679   12 VQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKV-TYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 69.21 E-value: 5.04e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1269 KLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAG--TVTA--RAGA 1343
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGkyTCVAtnSAGE 81


                   ....*....
gi 1883538138 1344 ADTSARLHV 1352
Cdd:pfam07679   82 AEASAELTV 90

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: 69.06 E-value: 6.55e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  251 APKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLS 330
Cdd:cd05744      6 APGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSF 85


                   ....*.
gi 1883538138  331 AVQLHV 336
Cdd:cd05744     86 NAELVV 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: 67.65 E-value: 1.42e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138 1009 LTCELSREDAPVRWYKDGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDAGDDSAFFTVTV 1074
Cdd:cd20967     17 LTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 66.76 E-value: 2.72e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138    18 PRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVA-SERLSFPEDGAEHGLLLSGALPTDAGVYVCRARNAAGEAYAA 96
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1883538138    97 AAVTV 101
Cdd:smart00410   81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.43 E-value: 2.92e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 64.57 E-value: 1.63e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  825 VRLTCEVDREDTTVHWYKDGQEVEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVAGDERAYFTVTI 892
Cdd:cd20967     15 IRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 64.45 E-value: 2.07e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1723 PREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVE-LCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA----GQDSAD 1796
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSG 80


                    ....*
gi 1883538138  1797 TQLLV 1801
Cdd:smart00410   81 TTLTV 85

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: 64.05 E-value: 3.20e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwDSSHFKLEpgrgasDEGASLTLRILAARLPDSGVY 207
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRP--DSAHKMLV------RENGRHSLIIEPVTKRDAGIY 72

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:cd05744     73 TCIARNRAGENSFNAELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 62.20 E-value: 9.81e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1266 PPVkLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARA 1341
Cdd:pfam13927    1 KPV-ITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 62.26 E-value: 1.05e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138 1096 PGH-VELRCEVAPAGSQVRWYKDGLEVEVSDALQLGAEGPARTLTLPHAQPEDAGEYVCETRDEAVTFNVSL 1166
Cdd:cd20967     11 KGHkIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 62.43 E-value: 1.25e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  251 APKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLS 330
Cdd:cd20990      6 APGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSF 85


                   ....*.
gi 1883538138  331 AVQLHV 336
Cdd:cd20990     86 NLELVV 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 62.27 E-value: 1.25e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1721 RPPREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA----GQDSA 1795
Cdd:pfam07679    5 QKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAEA 84


                   ....*.
gi 1883538138 1796 DTQLLV 1801
Cdd:pfam07679   85 SAELTV 90

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: 62.44 E-value: 1.36e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVWDSSHFKLEPGRGASdegaslTLRILAARLPDSGVY 207
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVH------VLHIRRVTVEDSAVY 74

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:cd20951     75 SAVAKNIHGEASSSASVVV 93

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: 62.02 E-value: 1.48e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWV-LRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdsshfklEPGRGASDEGaslTLRILAARLPDSGV 206
Cdd:cd20978      1 PKFIQKPEKNVVvKGGQDVTLPCQVTGVPQPKITWLHNGKPLQG---------PMERATVEDG---TLTIINVQPEDTGY 68

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd20978     69 YGCVATNEIGDIYTETLLHV 88

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: 61.58 E-value: 1.56e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   29 AELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASN 60

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: 61.75 E-value: 1.67e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1883538138   332 VQLHV 336
Cdd:smart00410   81 TTLTV 85

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: 61.67 E-value: 2.50e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASE---RLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

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: 60.59 E-value: 4.70e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  130 FLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALdEVWDSSHFKLEPGrgasdegaslTLRILAARLPDSGVYVC 209
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPL-LGKDERITTLENG----------SLQIKGAEKSDTGEYTC 70

                           90
                   ....*....|....*..
gi 1883538138  210 HARNAHGHAQAGALLQV 226
Cdd:cd20952     71 VALNLSGEATWSAVLDV 87

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 59.74 E-value: 1.15e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWvnEGKHAKFRCYVMGKPEPEIEWHLEGRPLLP--DRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTL 329
Cdd:cd20951      9 SHTVW--EKSDAKLRVEVQGKPDPEVKWYKNGVPIDPssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEAS 86


                   ....*...
gi 1883538138  330 SAVQLHVK 337
Cdd:cd20951     87 SSASVVVE 94

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: 59.44 E-value: 1.37e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1276 PLTVHEGDDATFQCEVS-PPDAEVTWLRNGAV-ITAGPQLEMVQNGSSRTLIIRGCQLKDAGT----VTARAGAADTSAR 1349
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTT 82


                    ...
gi 1883538138  1350 LHV 1352
Cdd:smart00410   83 LTV 85

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: 58.66 E-value: 2.43e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1277 LTVHEGDDATFQCEVSP-PDAEVTWLRNGAVITAGPQLEM-VQNGSSRTLIIRGCQLKDAG--TVTAR--AGAADTSARL 1350
Cdd:cd05744     10 LEVQEGRLCRFDCKVSGlPTPDLFWQLNGKPVRPDSAHKMlVRENGRHSLIIEPVTKRDAGiyTCIARnrAGENSFNAEL 89


                   ..
gi 1883538138 1351 HV 1352
Cdd:cd05744     90 VV 91

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: 58.11 E-value: 2.53e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  145 VVLTCQVGGLPEPKLYWEKDGMALDEvwdsshfklEPGRGASDEGASLTLRILAARLPDSGVYVCHARNAHG 216
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPP---------SSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

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: 58.41 E-value: 2.79e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  918 LTCELCRPWAEVRWTKDGEEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCEIHDESASFTITV 983
Cdd:cd20967     17 LTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 58.36 E-value: 2.94e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATN 78

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: 57.25 E-value: 5.75e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138 1279 VHEGDDATFQCEVSPPDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARAGAADTSARLHV 1352
Cdd:cd20967      9 VSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 57.46 E-value: 6.36e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  131 LTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdsshfkLEPGRGASDEGASLTLRILAARlpDSGVYVCH 210
Cdd:cd04978      3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEP--------APEDMRRTVDGRTLIFSNLQPN--DTAVYQCN 72

                           90
                   ....*....|....*.
gi 1883538138  211 ARNAHGHAQAGALLQV 226
Cdd:cd04978     73 ASNVHGYLLANAFLHV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 57.27 E-value: 7.31e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1539 IVQGPQDLEVTEGDTATFECELSQT-LADVIWEKDGQALSLSPRLRLQALGTRRLLLLRRCCSSDAGTYSCVV----GTA 1613
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTpDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEA 82


                   ....*....
gi 1883538138 1614 RSEpARLTV 1622
Cdd:pfam07679   83 EAS-AELTV 90

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: 57.10 E-value: 7.60e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  256 WVNEGKHAKFRCYVMGKPEPEIEW-HLEGRPLLPDRRRLMYRDRdggfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQL 334
Cdd:cd05764     11 RVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNG----TLDILITTVKDTGAFTCIASNPAGEATARVEL 86


                   ..
gi 1883538138  335 HV 336
Cdd:cd05764     87 HI 88

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: 56.48 E-value: 1.05e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1547 EVTEGDTATFECELSQTLADVIWEKDGQALSLSPRLRLQALGTRRLLLLRRCCSSDAGTYSCVVGTAR 1614
Cdd:cd20967      8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEK 75

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 56.42 E-value: 1.09e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGfVLKVLYCQAKDRGLYVCAARN 323
Cdd:pfam13927    8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 55.65 E-value: 1.90e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  804 PPVhIVNPQEHVFVHAITSecVRLTCEVDREDT-TVHWYKDGQEVEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVA 881
Cdd:pfam13927    1 KPV-ITVSPSSVTVREGET--VTLTCEATGSPPpTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 55.50 E-value: 3.36e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1269 KLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVIT---AGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARA--- 1341
Cdd:cd20951      2 EFIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDpssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAkni 81

                           90
                   ....*....|...
gi 1883538138 1342 -GAADTSARLHVR 1353
Cdd:cd20951     82 hGEASSSASVVVE 94

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.96 E-value: 5.73e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1628 SVLRELRSVSAREGDGATFECTVSET---EITgrWELGGRALRPGGRVRIRQEGKKHILVLSELRTEDTGEVCFQA---- 1700
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTpdpEVS--WFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsa 79

                           90
                   ....*....|.
gi 1883538138 1701 GPAQSLARLEV 1711
Cdd:pfam07679   80 GEAEASAELTV 90

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: 54.43 E-value: 6.41e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1180 PNPLCVVPGEPVVLSCELS-RASAQVFWSHNG-SPVQQGEGLELRAEGPRRILCIQAADLAHTGVYTCQSGASPGAPSLS 1257
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1883538138  1258 FNVQV 1262
Cdd:smart00410   81 TTLTV 85

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: 54.87 E-value: 7.21e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPD----RRRLMYRDRDGGFVLKVLYCQ--AKDRGLYVCAARNSA 325
Cdd:cd07693      7 PSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDkddpRSHRIVLPSGSLFFLRVVHGRkgRSDEGVYVCVAHNSL 86

                           90
                   ....*....|..
gi 1883538138  326 GQTLSA-VQLHV 336
Cdd:cd07693     87 GEAVSRnASLEV 98

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: 54.48 E-value: 9.66e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMAL--DEVWDSSHFKLEPgrgasdEGASLTLRILAARL--PD 203
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetDKDDPRSHRIVLP------SGSLFFLRVVHGRKgrSD 74

                           90       100
                   ....*....|....*....|....
gi 1883538138  204 SGVYVCHARNAHGHA-QAGALLQV 226
Cdd:cd07693     75 EGVYVCVAHNSLGEAvSRNASLEV 98

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: 54.16 E-value: 1.05e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   14 FLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEK-GGQQL-VASERL--SFPEDGAehgLLLSGALPTDAGVYVCRARNA 89
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKdGGTDFpAARERRmhVMPEDDV---FFIVDVKIEDTGVYSCTAQNS 78

                           90
                   ....*....|...
gi 1883538138   90 AGEAYAAAAVTVL 102
Cdd:cd05763     79 AGSISANATLTVL 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.80 E-value: 1.15e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138  825 VRLTCEVD-REDTTVHWYKDGQEVEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVA----GDERAYFTVTI 892
Cdd:pfam07679   18 ARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAEASAELTV 90

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: 53.55 E-value: 1.21e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  131 LTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALD----EVWDSShfklepgrgasdegaslTLRILAARLPDSGV 206
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPkgryEILDDH-----------------SLKIRKVTAGDMGS 63

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd05725     64 YTCVAENMVGKIEASATLTV 83

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: 53.10 E-value: 1.27e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  263 AKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDrDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 53.34 E-value: 1.45e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138  899 IVYPSSEVHVAAVrlERVVLTCELC-RPWAEVRWTKDGEEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCE 971
Cdd:pfam13927    4 ITVSPSSVTVREG--ETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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: 1.50e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138   14 FLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd20949      2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQ 76

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: 53.10 E-value: 1.51e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  825 VRLTCEVD-REDTTVHWYKDGQEVEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVA 881
Cdd:cd00096      1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

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: 53.10 E-value: 1.54e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1734 AVLEVTVS-RPGGHVCWMREGVELCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA 1790
Cdd:cd00096      1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.42 E-value: 1.58e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  342 RFTRPLQDVEGREHGIVVLECKV---PNSRIptAWFREDQRLLPCRKYEQIEEGAVRRLVIHKLKADDDGVYLCEMR--- 415
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVtgtPDPEV--SWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATnsa 79

                           90
                   ....*....|.
gi 1883538138  416 GRVRTVANVTV 426
Cdd:pfam07679   80 GEAEASAELTV 90

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: 53.01 E-value: 2.01e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  736 LTCELSRVDFPATWYKDGQKVEESESLIVKTEGRKHRLILPEAQVRDSGEFECRTEGVSAFFGVTV 801
Cdd:cd20967     17 LTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 53.35 E-value: 2.10e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd20973      9 VVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

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: 53.17 E-value: 2.17e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1541 QGPQDLEVTEGDTATFECELSQTLAD--VIWEKDGQALSLS-PRLRLQALGTRRLLLLRrccSSDAGTYSCV----VGTA 1613
Cdd:cd05724      2 VEPSDTQVAVGEMAVLECSPPRGHPEptVSWRKDGQPLNLDnERVRIVDDGNLLIAEAR---KSDEGTYKCVatnmVGER 78


                   ....*....
gi 1883538138 1614 RSEPARLTV 1622
Cdd:cd05724     79 ESRAARLSV 87

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: 52.89 E-value: 2.59e-08

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138   823 ECVRLTCEV-DREDTTVHWYKDGQE-VEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVA----GDERAYFTVTI 892
Cdd:smart00410   10 ESVTLSCEAsGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85

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: 52.96 E-value: 2.60e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138   23 VVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEH-GLLLSGALPTDAGVYVCRARN 88
Cdd:cd20973      9 VVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVN 75

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: 3.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  127 APKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGmalDEVWDSSHFKLepgrgaSDEGASLTLRILAARLPDSGV 206
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEG---KELQNSPDIQI------HQEGDLHSLIIAEAFEEDTGR 71

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd20972     72 YSCLATNSVGSDTTSAEIFV 91

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: 52.64 E-value: 3.77e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQL-VASERLSFPEDGAEhgLLLSGALPTDAGVYVCRARNA 89
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLqYAADRSTCEAGVGE--LHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|..
gi 1883538138   90 AGEAYAAAAVTV 101
Cdd:cd20976     79 AGQVSCSAWVTV 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: 52.51 E-value: 3.90e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  139 VLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVwDSSHFKLEPGRgasdegaslTLRILAARLPDSGVYVCHARN-AHGH 217
Cdd:cd20970     14 AREGENATFMCRAEGSPEPEISWTRNGNLIIEF-NTRYIVRENGT---------TLTIRNIRRSDMGIYLCIASNgVPGS 83


                   ....*....
gi 1883538138  218 AQAGALLQV 226
Cdd:cd20970     84 VEKRITLQV 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: 52.39 E-value: 4.10e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  255 FWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQL 334
Cdd:cd20969     12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDG-TLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90


                   ..
gi 1883538138  335 HV 336
Cdd:cd20969     91 HV 92

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: 52.45 E-value: 4.14e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLP---DRRRLMYRDrdggfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQ 333
Cdd:cd04978     11 LSPGETGELICEAEGNPQPTITWRLNGVPIEPapeDMRRTVDGR-----TLIFSNLQPNDTAVYQCNASNVHGYLLANAF 85


                   ...
gi 1883538138  334 LHV 336
Cdd:cd04978     86 LHV 88

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: 52.50 E-value: 4.14e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLS-FPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIARN 78

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 52.40 E-value: 4.26e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1099 VELRCEVAPAGSQVRWYKDGLEVEVSDALQLGAEGpaRTLTLPHAQPEDAGEYVCETRDEaVTFNVSL 1166
Cdd:cd05740     18 VTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGN--RTLTLLNVTREDAGAYQCEISNP-VSANRSD 82

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: 52.08 E-value: 6.01e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQL-VASERLSFPEDG-AEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqYNTDRISLYQDNcGRICLLIQNANKKDAGWYTVSAVN 79

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: 51.63 E-value: 6.36e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   18 PRPVRVVSGAEAELKCVV-LGEPPPTVVWEKGGQQLV-ASERLSFPEDGaehGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNlDNERVRIVDDG---NLLIAEARKSDEGTYKCVATN 73

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: 51.87 E-value: 6.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  127 APKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDevWDSSHFKLEPGRGasdegaslTLRILAARLPDSGV 206
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQ--YAADRSTCEAGVG--------ELHIQDVLPEDHGT 70

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd20976     71 YTCLAKNAAGQVSCSAWVTV 90

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: 51.47 E-value: 6.63e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1734 AVLEVTVSRPGGHVCWMREGVELCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQAGQDSADTQLLV 1801
Cdd:cd20967     15 IRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 51.18 E-value: 6.82e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1099 VELRCEVAPAGS-QVRWYKDGLEVEVSDALQLGAEGPARTLTLPHAQPEDAGEYVCE 1154
Cdd:cd00096      1 VTLTCSASGNPPpTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

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: 51.59 E-value: 8.31e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGfVLKVLYCQAKDRGLYVCAARNSAGQ 327
Cdd:cd05747     10 PRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKS-TFEISKVQMSDEGNYTVVVENSEGK 84

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: 51.35 E-value: 9.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  247 PLKGAPKTfwVNEGKHAKFRCYVMGKPEPEIEWHLEG-RPLLPDRRrlmYRDRDGGFVLKVLYCQAKDRGLYVCAARNSA 325
Cdd:cd20970      6 PQPSFTVT--AREGENATFMCRAEGSPEPEISWTRNGnLIIEFNTR---YIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80


                   ....*
gi 1883538138  326 GQTLS 330
Cdd:cd20970     81 PGSVE 85

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: 50.79 E-value: 1.06e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1285 ATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARA 1341
Cdd:cd00096      1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 51.10 E-value: 1.33e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138 1359 FLRRLQDVRAEEGQDVHLEVEtgrvgAAGT----VRWIRGGEPLPLDSRLTTAQDGHVHRLSIHGVLLTDQGTYGC 1430
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCT-----VTGTpdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73

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: 50.79 E-value: 1.49e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRL-MYRDRDGGFVL-KVlycQAKDRGLYVCAARNSAGQTLSAVQL 334
Cdd:cd20949     11 VKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMsKYRILADGLLInKV---TQDDTGEYTCRAYQVNSIASDMQER 87


                   ..
gi 1883538138  335 HV 336
Cdd:cd20949     88 TV 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 50.26 E-value: 1.74e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1722 PPREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA 1790
Cdd:pfam13927    7 SPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 50.55 E-value: 1.93e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd20975     12 VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 91

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: 50.28 E-value: 1.94e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVWDSSHFKLEPGrgasdegaslTLRILAARLPDSGVYVCHARN 213
Cdd:cd05867      6 PQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSSG----------ALILTDVQPSDTAVYQCEARN 75

                           90
                   ....*....|...
gi 1883538138  214 AHGHAQAGALLQV 226
Cdd:cd05867     76 RHGNLLANAHVHV 88

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: 50.47 E-value: 1.94e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   12 PCFLRFPRPVRVVSGAE-AELKCVVLGEPPPTVVWEKGGQQLVA-SERLSFpedgAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQdVTLPCQVTGVPQPKITWLHNGKPLQGpMERATV----EDGTLTIINVQPEDTGYYGCVATN 75

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: 50.72 E-value: 2.01e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  129 KFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMaldevwDSSHFKLEPGRGASDEGASLT--LRILAARLPDSGV 206
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGS------QNLLFPYQPPQPSSRFSVSPTgdLTITNVQRSDVGY 74

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd05726     75 YICQALNVAGSILAKAQLEV 94

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: 49.64 E-value: 2.14e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  916 VVLTCEL-CRPWAEVRWTKDGEEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCE 971
Cdd:cd00096      1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

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: 50.19 E-value: 2.29e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138   14 FLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQL-VASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLlGKDERITTLENGS---LQIKGAEKSDTGEYTCVALN 74

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: 50.08 E-value: 2.29e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDrdggFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd20978     13 VKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED----GTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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: 50.09 E-value: 2.30e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138   15 LRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASeRLSFPEDgaeHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDD---HSLKIRKVTAGDMGSYTCVAEN 70

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: 50.22 E-value: 2.36e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPlLPDRRRLMYRDRDggfVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKP-LGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQAT 83


                   ...
gi 1883538138  332 VQL 334
Cdd:cd20957     84 AEL 86

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: 50.55 E-value: 2.50e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  130 FLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVWDSSHFKLEpgrgasdEGASLTLRILAARL--PDSGVY 207
Cdd:cd05722      4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLP-------NGSLLITSVVHSKHnkPDEGFY 76


                   ....*.
gi 1883538138  208 VCHARN 213
Cdd:cd05722     77 QCVAQN 82

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 50.19 E-value: 2.87e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  518 PGPPVMVEMFKGQKNKVLLTWKPPEPPPETSFIYRLERQEVGSDDWIQC-FSIEKAGAVEVPGdcVPTEGDYHFRICTVS 596
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVeVTPGSETSYTLTG--LKPGTEYEFRVRAVN 78


                   ....*.
gi 1883538138  597 EHGRSP 602
Cdd:cd00063     79 GGGESP 84

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: 50.10 E-value: 2.88e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  139 VLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwDSSHFKLEpgrgaSDEGASLTLRILAARLPDSGVYVCHARNAHGHA 218
Cdd:cd05893     12 IFEGMPVTFTCRVAGNPKPKIYWFKDGKQISP--KSDHYTIQ-----RDLDGTCSLHTTASTLDDDGNYTIMAANPQGRI 84


                   ....*...
gi 1883538138  219 QAGALLQV 226
Cdd:cd05893     85 SCTGRLMV 92

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: 49.87 E-value: 3.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   11 PPcFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASER-LSFPeDGAehgLLLSGA-LPTDAGVYVCRARN 88
Cdd:cd20958      1 PP-FIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRqRVFP-NGT---LVIENVqRSSDEGEYTCTARN 75

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: 49.43 E-value: 3.45e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138   914 ERVVLTCEL-CRPWAEVRWTKDG-EEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCEIH----DESASFTITV 983
Cdd:smart00410   10 ESVTLSCEAsGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATnssgSASSGTTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 3.52e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  732 ERVVLTCELSRVDFP-ATWYKDGQKVEESESLIVKTEGRKHRLILPEAQVRDSGEFECR 789
Cdd:pfam07679   16 ESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 49.49 E-value: 3.65e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  725 SLTFTTSERVVLTCELSRVDFPA-TWYKDGQKVEESESLIVKTEGRKHRLILPEAQVRDSGEFECR 789
Cdd:pfam13927   10 SVTVREGETVTLTCEATGSPPPTiTWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 3.81e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1451 LRPLEDVTVHEGGSATFQLElsqegVTG------EWAQGGVRLHPGPKCHIQSEGRTHRLVLSGLGLADSG---CV---S 1518
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCT-----VTGtpdpevSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGkytCVatnS 78

                           90
                   ....*....|....
gi 1883538138 1519 FTADTlrCAARLTV 1532
Cdd:pfam07679   79 AGEAE--ASAELTV 90

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: 49.82 E-value: 3.89e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  135 QSQWVLRGEEVVLTCQ-VGGLPEPKLYWEKDGMALDEVwDSSHFKLEPGRGASDegasltLRILAARLPDSGVYVCHARN 213
Cdd:cd05750      7 KSQTVQEGSKLVLKCEaTSENPSPRYRWFKDGKELNRK-RPKNIKIRNKKKNSE------LQINKAKLEDSGEYTCVVEN 79

                           90
                   ....*....|...
gi 1883538138  214 AHGHAQAGALLQV 226
Cdd:cd05750     80 ILGKDTVTGNVTV 92

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: 49.91 E-value: 3.94e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  240 NPKPVLEPLKGAPKtfwvneGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVC 319
Cdd:cd05729      5 DTEKMEEREHALPA------ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTC 78


                   ....*...
gi 1883538138  320 AARNSAGQ 327
Cdd:cd05729     79 IVENEYGS 86

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 3.96e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138  914 ERVVLTCELC-RPWAEVRWTKDGEEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCEIHDE--SASFTITVT 984
Cdd:pfam07679   16 ESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSagEAEASAELT 89

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: 49.43 E-value: 4.00e-07

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  1099 VELRCEVAPAGS-QVRWYKDGLE-VEVSDALQLGAEGPARTLTLPHAQPEDAGEYVCETRDE 1158
Cdd:smart00410   12 VTLSCEASGSPPpEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

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: 49.43 E-value: 4.45e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  1005 ECVVLTCELSREDAP-VRWYKDGLE-VEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDA----GDDSAFFTVTV 1074
Cdd:smart00410   10 ESVTLSCEASGSPPPeVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85

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: 49.16 E-value: 5.52e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLP---DRRRLMYRDRDGGFVLKVlycQAKDRGLYVCAARNSAGqT 328
Cdd:cd05763      6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPaarERRMHVMPEDDVFFIVDV---KIEDTGVYSCTAQNSAG-S 81


                   ...
gi 1883538138  329 LSA 331
Cdd:cd05763     82 ISA 84

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 48.09 E-value: 7.73e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  358 VVLECKVPNSRIPTA-WFREDQRLLPCRKYEQIEEGAVRRLVIHKLKADDDGVYLCEMRGRVRTVANVTV 426
Cdd:cd00096      1 VTLTCSASGNPPPTItWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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: 48.73 E-value: 7.96e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1723 PREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA----GQDSADT 1797
Cdd:cd20972      8 LRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLAtnsvGSDTTSA 87


                   ....
gi 1883538138 1798 QLLV 1801
Cdd:cd20972     88 EIFV 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: 48.70 E-value: 8.54e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  255 FWVNEGK-----HA-------KFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAAR 322
Cdd:cd05857      2 YWTNPEKmekklHAvpaantvKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVE 81

                           90
                   ....*....|....
gi 1883538138  323 NSAGQTLSAVQLHV 336
Cdd:cd05857     82 NEYGSINHTYHLDV 95

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 48.33 E-value: 9.07e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  986 PPVrIIYPQDEVTLHAVSLecVVLTCELSREDAP-VRWYKDGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVC 1061
Cdd:pfam13927    1 KPV-ITVSPSSVTVREGET--VTLTCEATGSPPPtITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 48.33 E-value: 9.43e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1099 VELRCEVA--PAgSQVRWYKDGLEVEVSDALQLGAEGPARTLTLPHAQPEDAGEYVCE 1154
Cdd:pfam13927   19 VTLTCEATgsPP-PTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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: 48.39 E-value: 9.47e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1177 EAAPNPLCVVPGEPVVLSCELSRASAQVFWSHNGSPVQQGEGLELRAEGPRRILCIQAADLAHTGVYTCQSGASpgapSL 1256
Cdd:cd20967      1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGE----KC 76


                   ....*.
gi 1883538138 1257 SFNVQV 1262
Cdd:cd20967     77 SFELFV 82

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: 48.77 E-value: 9.64e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  142 GEEVVLTCQVGGLPEPKLYWEKDGMALDEVWDSSHFklepgrgaSDEGASLTlrILAARLPDSGVYVCHARNAHGHAQAG 221
Cdd:cd05730     18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSF--------NEDGSEMT--ILDVDKLDEAEYTCIAENKAGEQEAE 87


                   ....*
gi 1883538138  222 ALLQV 226
Cdd:cd05730     88 IHLKV 92

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: 48.40 E-value: 9.64e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  250 GAPKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGgfVLKVLYCQAKDRGLYVCAARNSAGQTL 329
Cdd:cd20976      6 SVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVG--ELHIQDVLPEDHGTYTCLAKNAAGQVS 83


                   ....*..
gi 1883538138  330 SAVQLHV 336
Cdd:cd20976     84 CSAWVTV 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: 48.70 E-value: 9.96e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEgrplLPDRRRLMYRDRD--GGFVLK-----VLY-CQAKDRGLYVCAARNSAG 326
Cdd:cd05765     12 VKVGETASFHCDVTGRPQPEITWEKQ----VPGKENLIMRPNHvrGNVVVTnigqlVIYnAQPQDAGLYTCTARNSGG 85

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: 47.96 E-value: 1.21e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDggfvLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd05723      4 PSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHN----LQVLGLVKSDEGFYQCIAENDVGNAQAS 79


                   ...
gi 1883538138  332 VQL 334
Cdd:cd05723     80 AQL 82

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: 48.17 E-value: 1.26e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQVG-GLPEPKLYWEKDGMALDEVwdsshfklEPGRGASDEGaslTLRILAARLPDSGVYVCHAR 212
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLD--------NERVRIVDDG---NLLIAEARKSDEGTYKCVAT 72


                   ....*
gi 1883538138  213 NAHGH 217
Cdd:cd05724     73 NMVGE 77

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: 47.97 E-value: 1.26e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRP---LLPDRRRlmyRDRDGGFVLKVLycQAKDRGLYVCAARNSAGQT 328
Cdd:cd05867      6 PQSHLYGPGETARLDCQVEGIPTPNITWSINGAPiegTDPDPRR---HVSSGALILTDV--QPSDTAVYQCEARNRHGNL 80


                   ....*...
gi 1883538138  329 LSAVQLHV 336
Cdd:cd05867     81 LANAHVHV 88

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.01 E-value: 1.30e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   16 RFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd20968      4 RPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS---LRIHNVQKEDAGQYRCVAKN 73

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: 47.95 E-value: 1.32e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  139 VLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHFKLEpgrgaSDEGASLTLRILAARLPDSGVYVCHARNAHGHA 218
Cdd:cd20973      9 VVEGSAARFDCKVEGYPDPEVKWMKDDNPIVE---SRRFQID-----QDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                   ....*...
gi 1883538138  219 QAGALLQV 226
Cdd:cd20973     81 TCSAELTV 88

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: 47.93 E-value: 1.50e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  142 GEEVVLTCQVGGLPEPKLYWEKDGMALDevwdsshfKLEPGRGASDEgasLTLRILAARLPDSGVYVCHARNAHGHAQA 220
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKPLT--------PPEIGENKKKK---WTLSLKNLKPEDSGKYTCHVSNRAGEINA 86

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: 47.96 E-value: 1.51e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  131 LTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGmalDEVWDSSHFKLEPGRgasdegaslTLRILAARLPDSGVYVCH 210
Cdd:cd05723      1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNG---DVVIPSDYFKIVKEH---------NLQVLGLVKSDEGFYQCI 68

                           90
                   ....*....|....*.
gi 1883538138  211 ARNAHGHAQAGALLQV 226
Cdd:cd05723     69 AENDVGNAQASAQLII 84

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 47.61 E-value: 1.66e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   518 PGPPVMVEMFKGQKNKVLLTWKPPEPPPETSFI--YRLERQEVGsDDWIQCFSIEKAGAVEVPGdcvPTEG-DYHFRICT 594
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIvgYRVEYREEG-SEWKEVNVTPSSTSYTLTG---LKPGtEYEFRVRA 76


                    ....*..
gi 1883538138   595 VSEHGRS 601
Cdd:smart00060   77 VNGAGEG 83

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: 47.80 E-value: 1.76e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1723 PREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCP---GNKYEMRRHGTTHSLVIHDVRPEDQGTYSCQA----GQDS 1794
Cdd:cd20951      7 LQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAknihGEAS 86


                   ....*..
gi 1883538138 1795 ADTQLLV 1801
Cdd:cd20951     87 SSASVVV 93

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: 47.50 E-value: 1.89e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   725 SLTFTTSERVVLTCELSRVDFPA-TWYKDGQK-VEESESLIVKTEGRKHRLILPEAQVRDSGEFEC--RTEGVSAFFGVT 800
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEvTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaaTNSSGSASSGTT 82


                    ..
gi 1883538138   801 VQ 802
Cdd:smart00410   83 LT 84

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: 47.45 E-value: 1.91e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   12 PCFLRFP--RPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd04969      1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAVN 76

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: 46.94 E-value: 1.92e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  734 VVLTCELSRVDFPA-TWYKDGQKVEESESLIVKTEGRKHRLILPEAQVRDSGEFECR 789
Cdd:cd00096      1 VTLTCSASGNPPPTiTWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

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: 46.94 E-value: 2.04e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1007 VVLTCELSREDAP-VRWYKDGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDA 1063
Cdd:cd00096      1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.18 E-value: 2.06e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1180 PNPLCVVPGEPVVLSCE-LSRASAQVFWSHNGSPVQQGEGLELRAEGPRRILCIQAADLAHTGVYTCQ 1246
Cdd:pfam13927    8 PSSVTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 47.25 E-value: 2.23e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138 1099 VELRCEVApaGS---QVRWYKDGLEVEVSDALQLGAEGPARTLTLPHAQPEDAGEYVCETRDEA--VTFNVSLA 1167
Cdd:pfam07679   18 ARFTCTVT--GTpdpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAgeAEASAELT 89

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: 47.50 E-value: 2.23e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1634 RSVSAREGDGATFECTVS-ETEITGRWEL-GGRALRPGGRVRIRQEGKKHILVLSELRTEDTG----EVCFQAGPAQSLA 1707
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGtytcAATNSSGSASSGT 81


                    ....
gi 1883538138  1708 RLEV 1711
Cdd:smart00410   82 TLTV 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 47.00 E-value: 3.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1721 RPPREKTVLVNRRAVLEVTV-SRPGGHVCWMREGVELcPGNKYEMRrhgTTHSLVIHDVRPEDQGTYSCQA----GQDSA 1795
Cdd:cd05725      2 KRPQNQVVLVDDSAEFQCEVgGDPVPTVRWRKEDGEL-PKGRYEIL---DDHSLKIRKVTAGDMGSYTCVAenmvGKIEA 77


                   ....*.
gi 1883538138 1796 DTQLLV 1801
Cdd:cd05725     78 SATLTV 83

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: 46.97 E-value: 3.14e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1535 VPVTIVQGPQDLEVTEGDTATFECELS-QTLADVIWEKDGQALSLSPRLRLQALGTRRLLLLRRCCSSDAGTYSCVV 1610
Cdd:cd05747      2 LPATILTKPRSLTVSEGESARFSCDVDgEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVV 78

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: 47.26 E-value: 3.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEG--------RPLLPDRRRLMYRDRDggfvLKVLYCQAKDRGLYVCAARN 323
Cdd:cd05726      6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKEGsqnllfpyQPPQPSSRFSVSPTGD----LTITNVQRSDVGYYICQALN 81

                           90
                   ....*....|....*
gi 1883538138  324 SAGQTLSAVQLHVKE 338
Cdd:cd05726     82 VAGSILAKAQLEVTD 96

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.87 E-value: 3.39e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1007 VVLTCELSREDAP-VRWYKDGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDA----GDDSAFFTVTV 1074
Cdd:pfam07679   18 ARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAEASAELTV 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: 47.16 E-value: 3.54e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKdgmaldEVWDSSHFKLEPG--RGASDEGASLTLRILAARLPDSG 205
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEK------QVPGKENLIMRPNhvRGNVVVTNIGQLVIYNAQPQDAG 74

                           90       100
                   ....*....|....*....|.
gi 1883538138  206 VYVCHARNAHGHAQAGALLQV 226
Cdd:cd05765     75 LYTCTARNSGGLLRANFPLSV 95

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: 46.80 E-value: 3.76e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1272 SELTPLTVHEGDDATFQCEVSP--PDAEVTWLRNGAVITAGPQLEMVQNGSSR-TLIIRGCQLKDAGTVTARA 1341
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTgsPGPDVTWSKEGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVV 73

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 46.62 E-value: 3.77e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138  916 VVLTCELCRPWAEVRWTKDGEEVVESPALLLEKEDtiRRLVLPSVQLEDSGEYLCEIHDE-----SASFTITV 983
Cdd:cd05740     18 VTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGN--RTLTLLNVTREDAGAYQCEISNPvsanrSDPVTLDV 88

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: 47.16 E-value: 3.83e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASErlsfPEDGAEHGLLLSGAL-----------PTDAG 80
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDK----DDPRSHRIVLPSGSLfflrvvhgrkgRSDEG 76


                   ....*...
gi 1883538138   81 VYVCRARN 88
Cdd:cd07693     77 VYVCVAHN 84

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: 46.69 E-value: 3.96e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDevWDSSHFKLEpgrgaSDEGASLTLRILAARLPDSGVY 207
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQ--YNTDRISLY-----QDNCGRICLLIQNANKKDAGWY 73

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:cd05892     74 TVSAVNEAGVVSCNARLDV 92

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: 46.97 E-value: 4.20e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASER 57
Cdd:cd05747      3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQR 49

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: 46.34 E-value: 4.43e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   348 QDVEGREHGIVVLECKVPNSRIPTA-WFREDQRLLPCR-KYEQIEEGAVRRLVIHKLKADDDGVYLCEMR---GRVRTVA 422
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVtWYKQGGKLLAESgRFSVSRSGSTSTLTISNVTPEDSGTYTCAATnssGSASSGT 81


                    ....
gi 1883538138   423 NVTV 426
Cdd:smart00410   82 TLTV 85

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: 46.73 E-value: 4.99e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1266 PPVKLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVqNGSSRTLIIRGCQLKDAGTVTARA 1341
Cdd:cd20970      1 PVISTPQPSFTVTAREGENATFMCRAEgSPEPEISWTRNGNLIIEFNTRYIV-RENGTTLTIRNIRRSDMGIYLCIA 76

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: 46.25 E-value: 5.73e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwDSSHFKLEPGRGASdegaSLTLRILAARlpDSGVY 207
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRP--DSAHKMLVRENGVH----SLIIEPVTSR--DAGIY 72

                           90
                   ....*....|
gi 1883538138  208 VCHARNAHGH 217
Cdd:cd20990     73 TCIATNRAGQ 82

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: 45.95 E-value: 6.67e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLmyRDRDGGfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd20952     11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERI--TTLENG-SLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 45.85 E-value: 7.50e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1272 SELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGssrTLIIRGCQLKDAGTVTARA----GAADT 1346
Cdd:cd20978      6 KPEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVAtneiGDIYT 82


                   ....*.
gi 1883538138 1347 SARLHV 1352
Cdd:cd20978     83 ETLLHV 88

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: 46.19 E-value: 7.93e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1267 PVKLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVT 1338
Cdd:cd05747      3 PATILTKPRSLTVSEGESARFSCDVDgEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYT 75

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 45.25 E-value: 1.05e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138  342 RFTRPLQDVEGREHGIVVLECKVPNSRIPT-AWFREDQRLLPCRKYEQIEEGAVRRLVIHKLKADDDGVYLCE 413
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTiTWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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: 45.08 E-value: 1.17e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPlLPDRRRLMYRDRDggfvLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd05725     12 DDSAEFQCEVGGDPVPTVRWRKEDGE-LPKGRYEILDDHS----LKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 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: 44.93 E-value: 1.20e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  259 EGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRdggfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSG----TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 45.39 E-value: 1.30e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGfVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd05738      6 PQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQLRSG-ALQIENSEESDQGKYECVATNSAGTRYSA 84


                   ....*..
gi 1883538138  332 -VQLHVK 337
Cdd:cd05738     85 pANLYVR 91

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: 45.27 E-value: 1.34e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1267 PVKLVSELTPLTVHEGDDATFQCEVSP-PDAEVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARA---- 1341
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGnPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLAtnsv 80

                           90
                   ....*....|.
gi 1883538138 1342 GAADTSARLHV 1352
Cdd:cd20972     81 GSDTTSAEIFV 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: 44.80 E-value: 1.53e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1543 PQDLEVTEGDTATFECELSQTLADVI-WEKDG-QALSLSPRLRLQALGTRRLLLLRRCCSSDAGTYSCVVGTAR---SEP 1617
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVtWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSgsaSSG 80


                    ....*
gi 1883538138  1618 ARLTV 1622
Cdd:smart00410   81 TTLTV 85

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: 44.89 E-value: 1.58e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   21 VRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFpEDGAEHGLLL-SGALPTDAGVYVCRARN 88
Cdd:cd05748      2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQI-ETTASSTSLViKNAKRSDSGKYTLTLKN 69

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: 45.15 E-value: 1.70e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwDSSHFKLEPgrgasdEGASLTLRILAARLPDSGVY 207
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRP--DQRRFAEEA------EGGLCRLRILAAERGDAGFY 72

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:cd20975     73 TCKAVNEYGARQCEARLEV 91

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: 44.10 E-value: 1.83e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   30 ELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05746      2 QIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGY---LAIRDVGVADQGRYECVARN 57

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: 44.88 E-value: 1.83e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQV-GGLPEPKLYWEKDGMALDEvwdSSHFKLEPGRGASdegASLTlrILAARLPDSGVYVCHAR 212
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIE---SLKVKHDNGRTTQ---SSLL--ISNVTKEDAGTYTCVVN 74


                   ....*...
gi 1883538138  213 NAHGHAQA 220
Cdd:pfam00047   75 NPGGSATL 82

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 45.00 E-value: 1.90e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEK--GGQ-----QLVASERLSFPEDGAehgLLLSGALPTDAGVYV 83
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTpgeykDLLYDPNVRILPNGT---LVFGHVQKENEGHYL 77


                   ....*
gi 1883538138   84 CRARN 88
Cdd:cd20954     78 CEAKN 82

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

Pssm-ID: 409551 Cd Length: 94 Bit Score: 44.79 E-value: 2.00e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  142 GEEVVLTCQV-GGLPEPKLYWEKDGMALDEVWDSSHFKLEPgrgasdEGASLTLRILAARlpDSGVYVCHARNAHGHAQA 220
Cdd:cd20959     17 GMRAQLHCGVpGGDLPLNIRWTLDGQPISDDLGITVSRLGR------RSSILSIDSLEAS--HAGNYTCHARNSAGSASY 88


                   ....*.
gi 1883538138  221 GALLQV 226
Cdd:cd20959     89 TAPLTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.48 E-value: 2.10e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138 1536 PVTIVQGPQDLEVTEGDTATFECE-LSQTLADVIWEKDGQALSLSPRLRLQALGTRRLLLLRRCCSSDAGTYSCVV 1610
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 44.10 E-value: 2.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  145 VVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHFKLEPgrgasdEGaslTLRILAARLPDSGVYVCHARNAHGHAQAGALL 224
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTE---SGKFHISP------EG---YLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 44.54 E-value: 2.25e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1366 VRAEEGQDVHLEVETGrvGAAGTVRWIRGGEPLPLDSRLTTAQDGHVHRLSIHGVLLTDQGTYGCESRHDRTLARLSV 1443
Cdd:cd20967      7 VQVSKGHKIRLTVELA--DPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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: 44.85 E-value: 2.33e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKggqQLVASERLSFPEDGAEHG--------LLLSGALPTDAGVYV 83
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEK---QVPGKENLIMRPNHVRGNvvvtnigqLVIYNAQPQDAGLYT 77


                   ....*
gi 1883538138   84 CRARN 88
Cdd:cd05765     78 CTARN 82

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: 44.13 E-value: 3.34e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138   18 PRPvrvvSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEH-GLLLSGALPTDAGVYVCRARN 88
Cdd:cd05729     15 ALP----AANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVEN 82

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: 43.86 E-value: 3.52e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMyrdrdGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHVK 337
Cdd:cd05851     16 GQNVTLECFALGNPVPVIRWRKILEPMPATAEISM-----SGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

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: 43.94 E-value: 3.72e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  136 SQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALdevwdsshfklePGRGASDEGASLTLRILAARLPDSGVYVCHARNAH 215
Cdd:cd05731      4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL------------PKGRTKFENFNKTLKIENVSEADSGEYQCTASNTM 71


                   ....
gi 1883538138  216 GHAQ 219
Cdd:cd05731     72 GSAR 75

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: 44.04 E-value: 4.15e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   21 VRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVA-SERLSFPEDGAEhgLLLSGALPTDAGVYVCRARN 88
Cdd:cd20970     12 VTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASN 78

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: 43.73 E-value: 4.28e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138 1077 PPERIVHPaaRSLDLQFGApgHVELRCEVA--PAgSQVRWYKDGLEVEVSDALQLGAEGPARTLTLPHAQPEDAGEYVC 1153
Cdd:cd20972      1 PPQFIQKL--RSQEVAEGS--KVRLECRVTgnPT-PVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSC 74

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: 43.54 E-value: 4.48e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  271 GKPEPEIEWHLEGRPLLPDRRRlmYRDRDGGFVLkVLYCQAKDRGLYVCAARNSAGQTLSAV 332
Cdd:cd05724     24 GHPEPTVSWRKDGQPLNLDNER--VRIVDDGNLL-IAEARKSDEGTYKCVATNMVGERESRA 82

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.84 E-value: 4.66e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKD-GMALDEVWDsshFKLEPGRGASDEGaslTLRILAARLPDSGV 206
Cdd:cd20954      2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAtGSTPGEYKD---LLYDPNVRILPNG---TLVFGHVQKENEGH 75

                           90
                   ....*....|
gi 1883538138  207 YVCHARNAHG 216
Cdd:cd20954     76 YLCEAKNGIG 85

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: 43.88 E-value: 5.26e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDevwdsshFKLEPGRGASDEGASLTLRILAARLPDSGVY 207
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIS-------TSTLPGVQISFSDGRAKLSIPAVTKANSGRY 73

                           90
                   ....*....|....*....
gi 1883538138  208 VCHARNAHGHAQAGALLQV 226
Cdd:cd20974     74 SLTATNGSGQATSTAELLV 92

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 43.54 E-value: 5.75e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  825 VRLTCEVDREDTTVHWYKDGQEVEESDIIVLENKGphHRLVLPAARPSDGGEFQCVAGDErayFTVTITDVFSWIVY 901
Cdd:cd05740     18 VTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGN--RTLTLLNVTREDAGAYQCEISNP---VSANRSDPVTLDVI 89

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: 43.70 E-value: 5.83e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138   19 RPVrvvsGAEAELKCVVLGEPPPTVVWEKGGQQLVASErlsfPEDGAEH--GLLLSGALPTDAGVYVCRARN 88
Cdd:cd05856     16 RPV----GSSVRLKCVASGNPRPDITWLKDNKPLTPPE----IGENKKKkwTLSLKNLKPEDSGKYTCHVSN 79

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: 43.29 E-value: 5.96e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALdevwdsshfklePGRGASDEGASLTLRILAARLPDSGVYVCHARN 213
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPL------------GHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

                           90
                   ....*....|...
gi 1883538138  214 AHGHAQAGALLQV 226
Cdd:cd20957     76 DGDSAQATAELKL 88

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: 43.40 E-value: 6.55e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVWdSSHFKLEpGRGASdegasltLRILAARLPDSGVYVCHARN 213
Cdd:cd05736      7 PEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKL-SKQLTLI-ANGSE-------LHISNVRYEDTGAYTCIAKN 77


                   ...
gi 1883538138  214 AHG 216
Cdd:cd05736     78 EGG 80

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: 43.38 E-value: 6.59e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  259 EGKHAKFRCYVMGKPEPEIEWhLEGRPLLPDRRRLMYRDRDGgfvLKVLYCQAKDRGLYVCAARNSAGQTLS 330
Cdd:cd20968     13 EGLKAVLPCTTMGNPKPSVSW-IKGDDLIKENNRIAVLESGS---LRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.77 E-value: 7.13e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138  825 VRLTCEVD-REDTTVHWYKDGQEVEesdiivlenkgPHHRLVLPAARPSDGGEFQCVAGDER-----AYFTVTI 892
Cdd:pfam13895   17 VTLTCSAPgNPPPSYTWYKDGSAIS-----------SSPNFFTLSVSAEDSGTYTCVARNGRggkvsNPVELTV 79

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: 43.40 E-value: 7.22e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138   26 GAEAELKCVVLGEPPPTVVWEKGGQQLVA--SERLSFPEDGAEhgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKNGMDINPklSKQLTLIANGSE--LHISNVRYEDTGAYTCIAKN 77

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: 43.00 E-value: 7.44e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   19 RPVRVVSGAEAELKCVVLGEPPPtVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRA 86
Cdd:cd20967      5 PAVQVSKGHKIRLTVELADPDAE-VKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVA 71

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 43.15 E-value: 7.86e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1883538138 1388 TVRWIRGGEPLPLDSRLTTAQDGHVhrLSIHGVLLTDQGTYGCESR 1433
Cdd:cd05740     30 SYLWWFNGQSLPVTPRLTLSNGNRT--LTLLNVTREDAGAYQCEIS 73

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: 42.95 E-value: 8.24e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   30 ELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEdgaEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05723     16 VFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVK---EHNLQVLGLVKSDEGFYQCIAEN 71

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: 42.94 E-value: 8.26e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDrdGGFVLKVLYcQAKDRGLYVCAARNSAGQTLSAvQLHVK 337
Cdd:cd20958     15 GQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPN--GTLVIENVQ-RSSDEGEYTCTARNQQGQSASR-SVFVK 88

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: 42.92 E-value: 8.38e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRlmyrdRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd04968      8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEI-----TTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQ 82


                   ....*
gi 1883538138  332 VQLHV 336
Cdd:cd04968     83 GRIIV 87

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: 42.99 E-value: 8.51e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQwvlrgeeVVLTCQVGGLPEPKLYWEKDGMALDEvwdsshfklepGRGA---SDEGASLTLRilAARLPDSGVYVCH 210
Cdd:cd05760     15 PSSR-------VTLRCHIDGHPRPTYQWFRDGTPLSD-----------GQGNysvSSKERTLTLR--SAGPDDSGLYYCC 74


                   ....*...
gi 1883538138  211 ARNAHGHA 218
Cdd:cd05760     75 AHNAFGSV 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.77 E-value: 8.84e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  131 LTGPQSQwVLRGEEVVLTCQVGGLPEPKLYWEKDGMALdevwdsshfklepgrgaSDEGASLTLRIlaaRLPDSGVYVCH 210
Cdd:pfam13895    4 LTPSPTV-VTEGEPVTLTCSAPGNPPPSYTWYKDGSAI-----------------SSSPNFFTLSV---SAEDSGTYTCV 62


                   ....*.
gi 1883538138  211 ARNAHG 216
Cdd:pfam13895   63 ARNGRG 68

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: 43.09 E-value: 8.94e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1277 LTVHEGDDATFQCEV---SPPDaeVTWLRNGAVITAGPQLEMVQNGSSRTLIIRGCQLKDAGTVTARA 1341
Cdd:cd20949      9 TTVKEGQSATILCEVkgePQPN--VTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 42.63 E-value: 1.03e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1180 PNPLCVVPGEPVVLSCELSRASA-QVFWSHNGSPVQQGEGLELRAEGPRRILCIQAADLAHTGVYTCQSGASPGAPSLSF 1258
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ....
gi 1883538138 1259 NVQV 1262
Cdd:pfam07679   87 ELTV 90

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: 42.73 E-value: 1.03e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  243 PVL-EPLKGApktfWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRR-RLMYRDRDGGFVLKVLYCQAKDRGLYVCA 320
Cdd:cd20974      1 PVFtQPLQSV----VVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLT 76

                           90
                   ....*....|....*..
gi 1883538138  321 ARNSAGQTLSAVQLHVK 337
Cdd:cd20974     77 ATNGSGQATSTAELLVL 93

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.38 E-value: 1.03e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  242 KPVLEPlkgaPKTFwVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRlmyrdrdggFVLKVLYCqakDRGLYVCAA 321
Cdd:pfam13895    1 KPVLTP----SPTV-VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNF---------FTLSVSAE---DSGTYTCVA 63

                           90
                   ....*....|....*.
gi 1883538138  322 RNSAGQTLSA-VQLHV 336
Cdd:pfam13895   64 RNGRGGKVSNpVELTV 79

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: 42.62 E-value: 1.16e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1267 PVKLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQLEMVQNGSSRtLIIRGCQLKDAGTVTA----RA 1341
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARgKPVPRITWIRNAQPLQYAADRSTCEAGVGE-LHIQDVLPEDHGTYTClaknAA 79

                           90
                   ....*....|.
gi 1883538138 1342 GAADTSARLHV 1352
Cdd:cd20976     80 GQVSCSAWVTV 90

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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 the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 42.21 E-value: 1.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWV-LRGEEVVLTCQVGGLPEPKLYWEK--DGMALDEVWDSSHFKlepgrgasdegaslTLRILAARLPDSGVYVCH 210
Cdd:cd05876      1 SSSSLVaLRGQSLVLECIAEGLPTPTVKWLRpsGPLPPDRVKYQNHNK--------------TLQLLNVGESDDGEYVCL 66


                   ....*....
gi 1883538138  211 ARNAHGHAQ 219
Cdd:cd05876     67 AENSLGSAR 75

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 43.09 E-value: 1.30e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  134 PQSQWVLRGEEVVLTCQV-GGLPEPKLYW--EKDGMALDEV--WDSSHFKLEPG-----RGASDEGASLTLRILAARLPD 203
Cdd:cd00099      5 PRSLSVQEGESVTLSCEVsSSFSSTYIYWyrQKPGQGPEFLiyLSSSKGKTKGGvpgrfSGSRDGTSSFSLTISNLQPED 84


                   ....*.
gi 1883538138  204 SGVYVC 209
Cdd:cd00099     85 SGTYYC 90

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: 42.44 E-value: 1.42e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1271 VSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVITAGPQlEMVQNGSSRTLIIRGCQLKDAGTVTARA----GAAD 1345
Cdd:cd04978      3 IIEPPSLVLSPGETGELICEAEgNPQPTITWRLNGVPIEPAPE-DMRRTVDGRTLIFSNLQPNDTAVYQCNAsnvhGYLL 81


                   ....*...
gi 1883538138 1346 TSARLHVR 1353
Cdd:cd04978     82 ANAFLHVL 89

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: 42.48 E-value: 1.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1721 RPPREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNKYEM-RRHGTTHSLVIHDVRPEDQGTYSC----QAGQDS 1794
Cdd:cd05744      5 QAPGDLEVQEGRLCRFDCKVSgLPTPDLFWQLNGKPVRPDSAHKMlVRENGRHSLIIEPVTKRDAGIYTCiarnRAGENS 84


                   ....*..
gi 1883538138 1795 ADTQLLV 1801
Cdd:cd05744     85 FNAELVV 91

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: 42.06 E-value: 1.50e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGP--QSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHFKLEPGRgasdegaslTLRILAARLPDSG 205
Cdd:cd04969      1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTN---SSRICILPDG---------SLKIKNVTKSDEG 68

                           90       100
                   ....*....|....*....|.
gi 1883538138  206 VYVCHARNAHGHAQAGALLQV 226
Cdd:cd04969     69 KYTCFAVNFFGKANSTGSLSV 89

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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 all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 42.57 E-value: 1.53e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1174 LAPEAAP-------NPLCVVPGEPVVLSCELSRASAQVFWSHNGSPVQQ-------GEGLELRAEGPRrilciqaadlaH 1239
Cdd:cd04973      3 LPPEAPPtyqisevESYSAHPGDLLQLRCRLRDDVQSINWTKDGVQLGEnnrtritGEEVQIKDAVPR-----------D 71

                           90       100
                   ....*....|....*....|...
gi 1883538138 1240 TGVYTCQSGASPGAPSLSFNVQV 1262
Cdd:cd04973     72 SGLYACVTSSPSGSDTTYFSVNV 94

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 42.20 E-value: 1.61e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  149 CQVGGLPEPKLYWEKDGMALDEvwdSSHFKLEPGrgasdegaslTLRILAARLPDSGVYVCHARNAHGHAQAGALLQV 226
Cdd:cd05728     21 CKASGNPRPAYRWLKNGQPLAS---ENRIEVEAG----------DLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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: 42.18 E-value: 1.64e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1541 QGPQDLEVTEGDTATFECELS--QTLADVIWEKDGQALSLSPRLRLQALGTRRLLLLRRCCS-SDAGTYSCVVGTARSEP 1617
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAStgSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTkEDAGTYTCVVNNPGGSA 80


                   ....
gi 1883538138 1618 ARLT 1621
Cdd:pfam00047   81 TLST 84

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: 42.06 E-value: 1.70e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1007 VVLTCELSREDAPVRWYKDGLEVEE--SEALVLQSDgprRRLVLPAAQPEDGGEFVCDAG 1064
Cdd:cd04979     14 VILSCSVKSNNAPVTWIHNGKKVPRyrSPRLVLKTE---RGLLIRSAQEADAGVYECHSG 70

Immunoglobulin (Ig)-like domain of the class IV semaphorin Sema4B; The members here are composed of the immunoglobulin (Ig)-like domain of Sema4B and similar proteins. Sema4B is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4B has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4B has been shown to preferentially regulate the development of the postsynaptic specialization at the glutamatergic synapses. This cytoplasmic domain includes a PDZ-binding motif upon which the synaptic localization of Sem4B is dependent. Sema4B is a ligand of CLCP1. CLCP1 was identified in an expression profiling analysis, which compared a highly metastic lung cancer subline with its low metastic parental line. Sema4B was shown to promote CLCP1 endocytosis and their interaction is a potential target for therapeutic intervention of metastasis.

Pssm-ID: 409456 Cd Length: 86 Bit Score: 42.04 E-value: 1.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1185 VVPGEPVVLSCELSRASAQVFWSHNGSPVQ-QGEGLELRAEGprriLCIQAADLAHTGVYTCQS---GASPGAPSLSFNV 1260
Cdd:cd05872      8 VVAGADVVLPCQLRSNLASPVWLFNGTPLNaQFSYLRLGTDG----LLILVTSPEHSGTYRCYSeeeGFQQLVASYSLNV 83


                   ..
gi 1883538138 1261 QV 1262
Cdd:cd05872     84 VE 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: 41.72 E-value: 1.88e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1364 QDVRAEEGQDVHLEVEtgrvgAAG----TVRWIR-GGEPLPLDSRLTTAQDGHVHRLSIHGVLLTDQGTYGCESRHDRTL 1438
Cdd:smart00410    2 PSVTVKEGESVTLSCE-----ASGspppEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 1883538138  1439 ----ARLSV 1443
Cdd:smart00410   77 assgTTLTV 85

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: 42.05 E-value: 1.95e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138   18 PRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQL-VASERLSFPEDGAEhgLLLSGALPTDAGVYVCRARN 88
Cdd:cd04978      6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIePAPEDMRRTVDGRT--LIFSNLQPNDTAVYQCNASN 75

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: 41.01 E-value: 2.19e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1747 VCWMREGVELCPGNKYEMRRHGTthsLVIHDVRPEDQGTYSCQA----GQDSADTQL 1799
Cdd:cd05746     15 ITWNKDGVQVTESGKFHISPEGY---LAIRDVGVADQGRYECVArntiGYASVSMVL 68

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: 41.16 E-value: 2.28e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1883538138 1388 TVRWIRGGEPLPLDSRLTTAQDGHVHRLSIHGVLLTDQGTYGCE 1431
Cdd:cd00096     14 TITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

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: 2.30e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   11 PPCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWE--KGG-----QQLVASE-RLSFPEDGAehgLLLSGALPTDAGVY 82
Cdd:cd05734      1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKhsKGSgvpqfQHIVPLNgRIQLLSNGS---LLIKHVLEEDSGYY 77


                   ....*.
gi 1883538138   83 VCRARN 88
Cdd:cd05734     78 LCKVSN 83

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: 41.80 E-value: 2.31e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   18 PRPVRVVSGAEAELKC-VVLGEPPPTVVWEKGGQQLVASERLSFPEDG-AEHGLLLSGALPTDAGVYVCRARN 88
Cdd:pfam00047    3 PPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHDNGRtTQSSLLISNVTKEDAGTYTCVVNN 75

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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 the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 41.44 E-value: 2.37e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  259 EGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRdggfVLKVLYCQAKDRGLYVCAARNSAG 326
Cdd:cd05876      9 RGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNK----TLQLLNVGESDDGEYVCLAENSLG 72

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: 41.62 E-value: 2.41e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  253 KTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRL-MYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSA 331
Cdd:cd05893      8 KHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYtIQRDLDGTCSLHTTASTLDDDGNYTIMAANPQGRISCT 87


                   ....*
gi 1883538138  332 VQLHV 336
Cdd:cd05893     88 GRLMV 92

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: 41.87 E-value: 2.42e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   14 FLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQ--------LVASERLSFPEDGaehGLLLSGALPTDAGVYVCR 85
Cdd:cd05726      2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnllfpyqpPQPSSRFSVSPTG---DLTITNVQRSDVGYYICQ 78


                   ...
gi 1883538138   86 ARN 88
Cdd:cd05726     79 ALN 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: 41.61 E-value: 2.46e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138 1185 VVPGEPVVLSCELSRA-SAQVFWSHNGSPVQQGEGLELRAEGPRRILCIQAADlahTGVYTCQSGASPGAPSLSFNVQV 1262
Cdd:cd20978     13 VKGGQDVTLPCQVTGVpQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPED---TGYYGCVATNEIGDIYTETLLHV 88

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 41.61 E-value: 2.59e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138 1548 VTEGDTATFECELSQTLADVIWEKDGQALSLSPRLRLQalGTRRLLLLRRCCSSDAGTYSC----VVGTARSEPARLTV 1622
Cdd:cd05740     12 VEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLS--NGNRTLTLLNVTREDAGAYQCeisnPVSANRSDPVTLDV 88

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: 41.68 E-value: 2.61e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  725 SLTFTTSERVVLTCELSRVDFPATWYKDGQKVEE--SESLIVKTEGrkhRLILPEAQVRDSGEFECRTEG-----VSAFF 797
Cdd:cd04979      5 QISVKEGDTVILSCSVKSNNAPVTWIHNGKKVPRyrSPRLVLKTER---GLLIRSAQEADAGVYECHSGErvlgsTLRSV 81


                   ....*..
gi 1883538138  798 GVTVQDP 804
Cdd:cd04979     82 TLHVLER 88

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: 41.62 E-value: 2.79e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   12 PCFLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLV--ASERLSFPEDGAeHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRpdSAHKMLVRENGV-HSLIIEPVTSRDAGIYTCIATN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.23 E-value: 3.07e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1543 PQDLEVTEGDTATFECELSQT-LADVIWEKDGQALSLSPRLRLQALGtrrllllrrccSSDAGTYSCVVGTAR----SEP 1617
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNpPPSYTWYKDGSAISSSPNFFTLSVS-----------AEDSGTYTCVARNGRggkvSNP 74


                   ....*
gi 1883538138 1618 ARLTV 1622
Cdd:pfam13895   75 VELTV 79

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: 3.33e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   26 GAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd20957     16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV---LVIPSVKREDKGMYQCFVRN 75

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: 41.43 E-value: 3.33e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   17 FPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEH-GLLLSGALPTDAGVYVCRARN 88
Cdd:cd05891      7 LPDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYaSLTIKGVTSEDSGKYSINVKN 79

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: 41.54 E-value: 3.34e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  133 GPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEVWDSSHFKLepgrgaSDEGAsltLRILAARLPDSGVYVCHAR 212
Cdd:cd05738      5 GPQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQ------LRSGA---LQIENSEESDQGKYECVAT 75


                   ....
gi 1883538138  213 NAHG 216
Cdd:cd05738     76 NSAG 79

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: 40.94 E-value: 3.38e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  142 GEEVVLTCQVGGLPEPKLYWEKDgmaldevWdsSHFKLEPGRGASDEGASLTLRILAARLPDSGVYVCHARNAHG 216
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLN-------W--GHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRG 66

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: 41.03 E-value: 3.45e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  825 VRLTCEV--DREDTTVHWYKDGQEVEESDIIVLENKGP-HHRLVLPAARPSDGGEFQCVA 881
Cdd:pfam00047   14 ATLTCSAstGSPGPDVTWSKEGGTLIESLKVKHDNGRTtQSSLLISNVTKEDAGTYTCVV 73

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: 41.39 E-value: 3.54e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   31 LKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLL-----LSGALPTDAGVYVCRARN 88
Cdd:cd20956     21 LKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGDVvsyvnISSVRVEDGGEYTCTATN 83

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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: 409452 Cd Length: 93 Bit Score: 41.19 E-value: 3.62e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  994 QDEVTLHAVSL---ECVVLTCELSREDAPVRWYK-DGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDAGD 1065
Cdd:cd05866      2 QVSISLSKVELsvgESKFFTCTAIGEPESIDWYNpQGEKIVSSQRVVVQKEGVRSRLTIYNANIEDAGIYRCQATD 77

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: 41.03 E-value: 3.62e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  914 ERVVLTCE--LCRPWAEVRWTKDGEEVVESpALLLEKEDTIRR--LVLPSVQLEDSGEYLCEIHDESASFTITVT 984
Cdd:pfam00047   12 DSATLTCSasTGSPGPDVTWSKEGGTLIES-LKVKHDNGRTTQssLLISNVTKEDAGTYTCVVNNPGGSATLSTS 85

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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: 409452 Cd Length: 93 Bit Score: 41.19 E-value: 4.03e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138   21 VRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEHGLLLSGALPTDAGVYVCRA 86
Cdd:cd05866     10 VELSVGESKFFTCTAIGEPESIDWYNPQGEKIVSSQRVVVQKEGVRSRLTIYNANIEDAGIYRCQA 75

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: 40.94 E-value: 4.09e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138 1540 VQGPQDLEVTEGDTATFECELSQT-LADVIWEKDGQALSLSPR-LRLQALGTRRLLLLRRCCSSDAGTYSCvvgTARSE 1616
Cdd:cd05744      4 LQAPGDLEVQEGRLCRFDCKVSGLpTPDLFWQLNGKPVRPDSAhKMLVRENGRHSLIIEPVTKRDAGIYTC---IARNR 79

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: 41.03 E-value: 4.36e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1084 PAARSLDLQFGapGHVELRCEVAPAGS--QVRWYKDGlevEVSDALQLGAEGPAR----TLTLPHAQPEDAGEYVCETRD 1157
Cdd:pfam00047    1 SAPPTVTVLEG--DSATLTCSASTGSPgpDVTWSKEG---GTLIESLKVKHDNGRttqsSLLISNVTKEDAGTYTCVVNN 75

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 40.86 E-value: 4.37e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  516 SPPGPPVMVEMfkgQKNKVLLTWKPPEPPPETSFIYRLERQEVGSDDWIQCFSIEK-AGAVEVPGDcvpTEG-DYHFRIC 593
Cdd:pfam00041    1 SAPSNLTVTDV---TSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGtTTSVTLTGL---KPGtEYEVRVQ 74


                   ....*....
gi 1883538138  594 TVSEHGRSP 602
Cdd:pfam00041   75 AVNGGGEGP 83

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 41.49 E-value: 4.70e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  130 FLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEV----WDSSHFKLEPGRGASDEGASLTLRILAARLPDSG 205
Cdd:cd20940      3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEIcsqlWDGARLDRVHINATYHQHATSTISIDNLTEEDTG 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  206 VYVCHARNahghaqagallqvhqpresppqDPDENpkpvlePLKGAPKTFWV 257
Cdd:cd20940     83 TYECRASN----------------------DPDRN------HLTRAPKVKWI 106

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: 41.04 E-value: 5.06e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138   18 PRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFP-EDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05737      8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKvEAGRTVYFTINGVSSEDSGKYGLVVKN 79

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: 40.69 E-value: 5.12e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138 1457 VTVHEGGSATFQLELSQEGVTGEWAQGGVRLHPGPKCHIQSEGRTHRLVLSGLGLADSGCVSFTADTLRCAARLTV 1532
Cdd:cd20967      7 VQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

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

Pssm-ID: 409417 Cd Length: 95 Bit Score: 41.07 E-value: 5.38e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  266 RCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGFVLKvlYCQAKDRGLYVCAARNSAGQTLS 330
Cdd:cd05760     22 RCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKERTLTLR--SAGPDDSGLYYCCAHNAFGSVCS 84

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 40.01 E-value: 5.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1191 VVLSCELS-RASAQVFWSHNGSPVQQGEGLELRAEGPRRILCIQAADLAHTGVYTCQ 1246
Cdd:cd00096      1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

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: 40.87 E-value: 5.74e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  805 PVHIVNPQEH-VFvhaiTSECVRLTCEVDRE-DTTVHWYKDGQEVEESDII---VLENKGPHHRLVLPAARPSDGGEFQC 879
Cdd:cd20951      1 PEFIIRLQSHtVW----EKSDAKLRVEVQGKpDPEVKWYKNGVPIDPSSIPgkyKIESEYGVHVLHIRRVTVEDSAVYSA 76


                   ..
gi 1883538138  880 VA 881
Cdd:cd20951     77 VA 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 40.24 E-value: 6.30e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1364 QDVRAEEGQDVHLEVETGRVGAAgTVRWIRGGEPLPLDSRLTTAQDGHVHRLSIHGVLLTDQGTYGCE 1431
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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: 40.52 E-value: 6.81e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138 1093 FGAPGHVELRCEVAPAGSQVRWYKDGLEVE--VSDALQLGAEgpaRTLTLPHAQPEDAGEYVCE 1154
Cdd:cd04979      8 VKEGDTVILSCSVKSNNAPVTWIHNGKKVPryRSPRLVLKTE---RGLLIRSAQEADAGVYECH 68

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: 40.52 E-value: 6.86e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  257 VNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRL-MYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLH 335
Cdd:cd05892     12 VLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRIsLYQDNCGRICLLIQNANKKDAGWYTVSAVNEAGVVSCNARLD 91


                   .
gi 1883538138  336 V 336
Cdd:cd05892     92 V 92

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: 7.21e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138  917 VLTCELC-RPWAEVRWTKDGEEVVESPALLLEKEDtirRLVLPSVQLEDSGEYLCEIHDESASFTIT 982
Cdd:cd20957     20 VFNCSVTgNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQAT 83

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

Pssm-ID: 409410 [Multi-domain] Cd Length: 79 Bit Score: 40.04 E-value: 7.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  727 TFTTSERVVLTCE--LSRVDFPATWYKDGQKVEESESLIVktegrkhrliLPEAQVRDSGEFECRTEGVSaffgvtvQDP 804
Cdd:cd05752     11 TVFQGEKVTLTCQgfYSPEQNSTQWYHNGTLISSTSSSYR----------IVAATVNDSGEYRCQTQGSS-------LSD 73


                   ....
gi 1883538138  805 PVHI 808
Cdd:cd05752     74 PVHL 77

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: 40.09 E-value: 7.73e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1883538138  267 CYVMGKPEPEIEWHLEGRPLLPDRRRLmyrdRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHVK 337
Cdd:cd05731     17 CIAEGLPTPDIRWIKLGGELPKGRTKF----ENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTVE 83

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: 7.97e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRlMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHVKE 338
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKLSK-QLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 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: 39.88 E-value: 8.19e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1294 PDAEVTWLRNGAVITAgPQLEMVQNGSSRT-LIIRGCQLKDAG--TVTARAGAADTSARLHVR 1353
Cdd:cd05748     20 PTPTVTWSKDGQPLKE-TGRVQIETTASSTsLVIKNAKRSDSGkyTLTLKNSAGEKSATINVK 81

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: 40.08 E-value: 8.34e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138 1720 RRPPREKTVLVNRRAVLEVtvSRPGGH----VCWMREGVELcpgNKYEMRRHGTTH-SLVIHDVRPEDQGTYSCQA 1790
Cdd:cd05724      1 RVEPSDTQVAVGEMAVLEC--SPPRGHpeptVSWRKDGQPL---NLDNERVRIVDDgNLLIAEARKSDEGTYKCVA 71

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: 40.18 E-value: 8.55e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  1455 EDVTVHEGGSATFQLELSQEG-VTGEWA-QGGVRLHPGPKCHIQSEGRTHRLVLSGLGLADSG---C-VSFTADTLRCAA 1528
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPpPEVTWYkQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGtytCaATNSSGSASSGT 81


                    ....
gi 1883538138  1529 RLTV 1532
Cdd:smart00410   82 TLTV 85

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: 40.30 E-value: 8.65e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  258 NEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDrDGGfVLKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd05730     16 NLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNE-DGS-EMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 39.87 E-value: 9.46e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  825 VRLTCEVDREDT-TVHWYKDGQEVEESDIIVLENKGPHHRLVLPAARPSDGGEFQCVA 881
Cdd:cd20972     19 VRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 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: 39.82 E-value: 1.02e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138   18 PRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASE-RLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05894      2 ENTIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgRVRVESYKDLSSFVIEGAEREDEGVYTITVTN 73

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: 39.77 E-value: 1.16e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  138 WVLRGEEVVLTCQVGGLPEPKLYW-EKDGmaldevwdsshfKLEPGRGASDEGASLTLRILAARLPDSGVYVCHARNAHG 216
Cdd:cd05764     11 RVLEGQRATLRCKARGDPEPAIHWiSPEG------------KLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAG 78


                   ....
gi 1883538138  217 HAQA 220
Cdd:cd05764     79 EATA 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: 39.84 E-value: 1.19e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRrrlMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQ 327
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPE---IGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 39.46 E-value: 1.22e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1358 LFLRRLQDVRaeEGQDVHLEVETGRVGAAGTVRWIRGGEPLPldsrlTTAQDGHvHRLSIHGVLLTDQGTYGCESRHDRT 1437
Cdd:cd05754      5 VEEPRSQEVR--PGADVSFICRAKSKSPAYTLVWTRVNGTLP-----SRAMDFN-GILTIRNVQLSDAGTYVCTGSNMLD 76


                   ..
gi 1883538138 1438 LA 1439
Cdd:cd05754     77 TD 78

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 39.40 E-value: 1.25e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1180 PNPLCVVPGEPVVLSCE-LSRASAQVFWSHNGSPVQQGEGLELRAEGPRrilciqaadlaHTGVYTCQSGASPGAP--SL 1256
Cdd:cd20948      2 PSDTYYLSGENLNLSCHaASNPPAQYSWTINGTFQTSSQELFLPAITEN-----------NEGTYTCSAHNSLTGKniSL 70


                   ....*.
gi 1883538138 1257 SFNVQV 1262
Cdd:cd20948     71 VLSVTV 76

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: 39.64 E-value: 1.32e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138  924 RPWAEVRWTKDGE--EVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCEIHDESASFTITVT 984
Cdd:cd20974     27 KPVPEVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATSTAE 89

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: 39.44 E-value: 1.32e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138 1270 LVSELTP--LTVHEGDDATFQCEVSP-PDAEVTWLRNGAVITAGpqlEMVQNGSSRTLIIRGCQLKDAG 1335
Cdd:cd20957      2 LSATIDPpvQTVDFGRTAVFNCSVTGnPIHTVLWMKDGKPLGHS---SRVQILSEDVLVIPSVKREDKG 67

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: 39.58 E-value: 1.59e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  267 CYVMGKPEPEIEWHLEGRPLLPDRRRLmyrdrDGGFVLK---------VLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd05869     24 CEASGDPIPSITWRTSTRNISSEEKTL-----DGHIVVRsharvssltLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

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: 39.47 E-value: 1.60e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  127 APKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHFKLEPGRGASDEGASLtLRILAARLPDSGV 206
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPE---SPRFRVGDYVTSDGDVVSY-VNISSVRVEDGGE 76

                           90       100
                   ....*....|....*....|
gi 1883538138  207 YVCHARNAHGHAQAGALLQV 226
Cdd:cd20956     77 YTCTATNDVGSVSHSARINV 96

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: 39.38 E-value: 1.70e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138   14 FLRFPRPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQ--QLVASERLSFPEDGAehgLLLSGALPT-----DAGVYVCRA 86
Cdd:cd05722      4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGS---LLITSVVHSkhnkpDEGFYQCVA 80


                   ..
gi 1883538138   87 RN 88
Cdd:cd05722     81 QN 82

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: 39.12 E-value: 1.75e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   26 GAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFpEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV-EAGD---LRITKLSLSDSGMYQCVAEN 72

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: 39.42 E-value: 1.81e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  732 ERVVLTCELSRvDFPA---TWYKDGQKVEESESLIVKTEGRK--HRLILPEAQVRDSGEFECRTE 791
Cdd:cd05750     15 SKLVLKCEATS-ENPSpryRWFKDGKELNRKRPKNIKIRNKKknSELQINKAKLEDSGEYTCVVE 78

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: 39.41 E-value: 1.89e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  346 PLQDVEGREHGIVVLECKVPNSRIPT-AWFRED-QRLLPCRKYEQIEEGavRRLVIHKLKADDDGVYLC 412
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEiSWTRNGnLIIEFNTRYIVRENG--TTLTIRNIRRSDMGIYLC 74

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: 39.23 E-value: 1.92e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138   19 RPVRVVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSfpedgaehgllLSGAL-------PTDAGVYVCRARN 88
Cdd:cd05851      9 KDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEIS-----------MSGAVlkifniqPEDEGTYECEAEN 74

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.92 E-value: 2.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1175 APEAAPNPLCVVPGEPVVLSCELS-RASAQVFWSHNGSPVQQGeglelraegprRILCIQAADLAHTGVYTCQSGASPGA 1253
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPgNPPPSYTWYKDGSAISSS-----------PNFFTLSVSAEDSGTYTCVARNGRGG 69

                           90
                   ....*....|
gi 1883538138 1254 -PSLSFNVQV 1262
Cdd:pfam13895   70 kVSNPVELTV 79

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: 39.03 E-value: 2.04e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  914 ERVVLTCELC--RPWAEVRWTKDGEEVVESPAllleKEDTIR------RLVLPSVQLEDSGEYLCEIHD----ESASFTI 981
Cdd:cd05750     15 SKLVLKCEATseNPSPRYRWFKDGKELNRKRP----KNIKIRnkkknsELQINKAKLEDSGEYTCVVENilgkDTVTGNV 90


                   ..
gi 1883538138  982 TV 983
Cdd:cd05750     91 TV 92

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: 39.12 E-value: 2.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  139 VLRGEEVVLTCQVGGLPEPKLYWEKDGMALDEvwdSSHF--KLEPGRGASdegasltLRILAARLPDSGVYVCHARNAHG 216
Cdd:cd05891     13 IMEGKTLNLTCTVFGNPDPEVIWFKNDQDIEL---SEHYsvKLEQGKYAS-------LTIKGVTSEDSGKYSINVKNKYG 82

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: 39.09 E-value: 2.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1721 RPPREKTVLVNRRAVLEVTVsrpGGH----VCWMREGVELcPGNkyemRRH-----GTthsLVIHDV-RPEDQGTYSCQA 1790
Cdd:cd20958      5 RPMGNLTAVAGQTLRLHCPV---AGYpissITWEKDGRRL-PLN----HRQrvfpnGT---LVIENVqRSSDEGEYTCTA 73

                           90
                   ....*....|....*.
gi 1883538138 1791 ----GQ-DSADTQLLV 1801
Cdd:cd20958     74 rnqqGQsASRSVFVKV 89

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: 39.03 E-value: 2.25e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138 1008 VLTCELSRED-AP-VRWYKDGLEV--EESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDA----GDDSAFFTVTV 1074
Cdd:cd05750     18 VLKCEATSENpSPrYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVenilGKDTVTGNVTV 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: 38.83 E-value: 2.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVL--RGEEVVLTCQVGGLPEPKLYWEKDGMALDE-----VWDSShfklepgrgasdegaslTLRILAAR 200
Cdd:cd05852      1 PTFEFNPMKKKILaaKGGRVIIECKPKAAPKPKFSWSKGTELLVNnsrisIWDDG-----------------SLEILNIT 63

                           90       100
                   ....*....|....*....|....*.
gi 1883538138  201 LPDSGVYVCHARNAHGHAQAGALLQV 226
Cdd:cd05852     64 KLDEGSYTCFAENNRGKANSTGVLSV 89

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: 38.87 E-value: 2.39e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1538 TIVQGPQDLEVTEGDTATFECELS-QTLADVIWEKDGQALSLS--PRLRLQALGTRRLLLLRRCCSSDAGTYS 1607
Cdd:cd20974      2 VFTQPLQSVVVLEGSTATFEAHVSgKPVPEVSWFRDGQVISTStlPGVQISFSDGRAKLSIPAVTKANSGRYS 74

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: 39.07 E-value: 2.40e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1538 TIVQGPQDLEVTEGDTATFECELSQTLADVI-WEKDGQAL---SLSPRLR-----------LQALGTRRLLllrrccsSD 1602
Cdd:cd07693      2 RIVEHPSDLIVSKGDPATLNCKAEGRPTPTIqWLKNGQPLetdKDDPRSHrivlpsgslffLRVVHGRKGR-------SD 74

                           90       100
                   ....*....|....*....|....
gi 1883538138 1603 AGTYSCV----VGTARSEPARLTV 1622
Cdd:cd07693     75 EGVYVCVahnsLGEAVSRNASLEV 98

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

Pssm-ID: 409551 Cd Length: 94 Bit Score: 39.01 E-value: 2.43e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1188 GEPVVLSCELSRAS--AQVFWSHNGSPVQQGEGLELRAEGPR-RILCIQAADLAHTGVYTCQSGASPGAPSLSFNVQV 1262
Cdd:cd20959     17 GMRAQLHCGVPGGDlpLNIRWTLDGQPISDDLGITVSRLGRRsSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

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: 2.49e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  142 GEEVVLTCQVGGLPEPKLYWEKDGMALDevWDSSHFKLEPGrgasdegaslTLRILAARLPDSGVYVCHARNAHGHAQAG 221
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLS--VDRRHLVLSSG----------TLRISRVALHDQGQYECQAVNIVGSQRTV 69


                   ....*
gi 1883538138  222 ALLQV 226
Cdd:cd05745     70 AQLTV 74

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: 38.72 E-value: 2.56e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138 1722 PPREKTVLVNRRAVL--EVTVSRPGGHVCWMREGVELCPGNKY-EMRRHGTTHSLVIHDVRPEDQGTYSCQA 1790
Cdd:pfam00047    2 APPTVTVLEGDSATLtcSASTGSPGPDVTWSKEGGTLIESLKVkHDNGRTTQSSLLISNVTKEDAGTYTCVV 73

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: 38.53 E-value: 2.78e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1722 PPREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNKyemRRHGTTHSLVIHDVRPEDQGTYSCQA 1790
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPME---RATVEDGTLTIINVQPEDTGYYGCVA 73

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: 2.89e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138   23 VVSGAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAEH-GLLLSGALPTDAGVYVCRARN 88
Cdd:cd05857     16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHwSLIMESVVPSDKGNYTCVVEN 82

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: 38.34 E-value: 2.90e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  924 RPWAEVRWTKDGEEVVESPALLLEKEDTIRRLVLPSVQLEDSGEYLCEIHDES--ASFTITV 983
Cdd:cd05748     19 RPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAgeKSATINV 80

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: 38.72 E-value: 3.27e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  252 PKTFWVNEGKHAKFRCYVMGKPEPEIEWHLEGRPL--LPDrrrlmYRDRDGGFVLKVLYCQA--KDRGLYVCAARNSAGQ 327
Cdd:cd20972      8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELqnSPD-----IQIHQEGDLHSLIIAEAfeEDTGRYSCLATNSVGS 82


                   ....*....
gi 1883538138  328 TLSAVQLHV 336
Cdd:cd20972     83 DTTSAEIFV 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.14 E-value: 3.56e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1269 KLVSELTPLTVHEGDDATFQCEVS-PPDAEVTWLRNGAVItagpqlemvqnGSSRTLIIRGCQLKDAGTVTARAGAADTS 1347
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPgNPPPSYTWYKDGSAI-----------SSSPNFFTLSVSAEDSGTYTCVARNGRGG 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: 38.54 E-value: 3.56e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138  143 EEVVLTCQVGGLPEPKLYWEKDGmaldevwdsSHFKLEPGRGASDEGASLTLRILAARLPDS---GVYVCHARNAHGHA 218
Cdd:cd05733     17 DNITIKCEAKGNPQPTFRWTKDG---------KFFDPAKDPRVSMRRRSGTLVIDNHNGGPEdyqGEYQCYASNELGTA 86

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: 38.31 E-value: 3.61e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  266 RCYVMGKPEPEIEWHLEGRPLLPDRRRLM--YRDRDGGFV--LKVLYCQAKDRGLYVCAARNSAGQTLSAVQLHV 336
Cdd:cd20956     22 KCVASGNPLPQITWTLDGFPIPESPRFRVgdYVTSDGDVVsyVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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: 38.28 E-value: 3.62e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1883538138 1536 PVTIVQGPQDLEVTEGDTATFECELS-QTLADVIWEKDGQALSLSPRLRLQALGTRRLLLLRrccSSDAGTYSCVVG 1611
Cdd:cd20957      1 PLSATIDPPVQTVDFGRTAVFNCSVTgNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVK---REDKGMYQCFVR 74

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: 38.35 E-value: 3.75e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  142 GEEVVLTCQVGGLPEPKLYWEKDGMaldEVWdsSHFKLEPGRgASDEGASLTLRILAARlpDSGVYVCHARNAHG 216
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGK---EFK--KEHRIGGTK-VEEKGWSLIIERAIPR--DKGKYTCIVENEYG 85

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

Pssm-ID: 409551 Cd Length: 94 Bit Score: 38.24 E-value: 3.81e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  258 NEGKHAKFRCYVMGKPEP-EIEWHLEGRPLLPDR----RRLMYRdrdgGFVLKVLYCQAKDRGLYVCAARNSAGQTLSAV 332
Cdd:cd20959     15 QVGMRAQLHCGVPGGDLPlNIRWTLDGQPISDDLgitvSRLGRR----SSILSIDSLEASHAGNYTCHARNSAGSASYTA 90


                   ....
gi 1883538138  333 QLHV 336
Cdd:cd20959     91 PLTV 94

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: 37.85 E-value: 3.84e-03

                           10        20
                   ....*....|....*....|....*...
gi 1883538138 1763 EMRRHGTTHSLVIHDVRPEDQGTYSCQA 1790
Cdd:cd05743     34 SITSEGGYGTLTIRDVKESDQGAYTCEA 61

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: 38.26 E-value: 3.89e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1883538138 1722 PPREKTVLVNRRAVLEVTVS-RPGGHVCWMREGVELCPGNK-YEMRRHGTThsLVIHDVRPEDQGTYSCQA 1790
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEgSPEPEISWTRNGNLIIEFNTrYIVRENGTT--LTIRNIRRSDMGIYLCIA 76

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: 37.61 E-value: 4.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1370 EGQDVHLEVEtgrvgAAG----TVRWIRGGEPLPLDSRLTTAQDGhvhRLSIHGVLLTDQGTYGCESRH----DRTLARL 1441
Cdd:cd05745      1 EGQTVDFLCE-----AQGypqpVIAWTKGGSQLSVDRRHLVLSSG---TLRISRVALHDQGQYECQAVNivgsQRTVAQL 72


                   ..
gi 1883538138 1442 SV 1443
Cdd:cd05745     73 TV 74

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: 38.15 E-value: 4.05e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138  358 VVLECKVPNSRIPTA-WFREDQRLlPCRKYEQIEEgavRRLVIHKLKADDDGVYLCE---MRGRVRTVANVTV 426
Cdd:cd05725     15 AEFQCEVGGDPVPTVrWRKEDGEL-PKGRYEILDD---HSLKIRKVTAGDMGSYTCVaenMVGKIEASATLTV 83

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: 37.94 E-value: 4.06e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138  721 QDKVSLTFTTSERVVLTCELSRVDFPA--TWYKDGQKVEESEsLIVKTEGRKHR--LILPEAQVRDSGEFECRT 790
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGPdvTWSKEGGTLIESL-KVKHDNGRTTQssLLISNVTKEDAGTYTCVV 73

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: 38.15 E-value: 4.07e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  812 QEHVFVHAITSECVRLTCEVDR--EDTTVHWYKDGQEVEESDIIVLENKGphHRLVLPAARPSDGGEFQCVA 881
Cdd:cd05724      2 VEPSDTQVAVGEMAVLECSPPRghPEPTVSWRKDGQPLNLDNERVRIVDD--GNLLIAEARKSDEGTYKCVA 71

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: 38.32 E-value: 4.07e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138  820 ITSECVRLTCEVDRE-DTTVHWYKDGQEVEESDIIVLENKGPHH-RLVLPAARPSDGGEFQCVA 881
Cdd:cd20973     10 VEGSAARFDCKVEGYpDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKA 73

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: 4.24e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138 1720 RRPPREKTVLVNRRAVLE-VTVSRPGGHVCWMREGVELCPGNKYEMRRHGtthSLVIHDVRPEDQGTYSCQA 1790
Cdd:cd20968      3 TRPPTNVTIIEGLKAVLPcTTMGNPKPSVSWIKGDDLIKENNRIAVLESG---SLRIHNVQKEDAGQYRCVA 71

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: 38.25 E-value: 4.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1630 LRELRSVSAREGDGATFECTVSET---EITgrWELGGRALRPGGR-VRIRQEGKKHILVLSELRTEDTGEV-CF---QAG 1701
Cdd:cd05744      4 LQAPGDLEVQEGRLCRFDCKVSGLptpDLF--WQLNGKPVRPDSAhKMLVRENGRHSLIIEPVTKRDAGIYtCIarnRAG 81

                           90
                   ....*....|
gi 1883538138 1702 PAQSLARLEV 1711
Cdd:cd05744     82 ENSFNAELVV 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 4.60e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1883538138  914 ERVVLTCEL-CRPWAEVRWTKDGEEVVESPalllekedtirRLVLPSVQLEDSGEYLCEIHDE-----SASFTITV 983
Cdd:pfam13895   15 EPVTLTCSApGNPPPSYTWYKDGSAISSSP-----------NFFTLSVSAEDSGTYTCVARNGrggkvSNPVELTV 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: 37.95 E-value: 4.79e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138  725 SLTFTTSERVVLTCELSRVDFPAT-WYKDGQKVEESESLIVKTEGRKHRLILPEAQVRDSGEFEC 788
Cdd:cd20972     10 SQEVAEGSKVRLECRVTGNPTPVVrWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSC 74

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: 37.76 E-value: 4.88e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1099 VELRCEVA--PAgSQVRWYKDGLEVEVSDALQLgaegPARTLTLPHAQPEDAGEYVCE 1154
Cdd:cd05725     15 AEFQCEVGgdPV-PTVRWRKEDGELPKGRYEIL----DDHSLKIRKVTAGDMGSYTCV 67

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: 37.76 E-value: 5.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  908 VAAVRLERVVLTCELC-RPWAEVRWTKDGEEVVESPALLLEKEDTirrLVLPSVQLEDSGEYLC----EIHDESASFTIT 982
Cdd:cd20978     11 VVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPMERATVEDGT---LTIINVQPEDTGYYGCvatnEIGDIYTETLLH 87


                   .
gi 1883538138  983 V 983
Cdd:cd20978     88 V 88

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: 37.67 E-value: 5.91e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   12 PCFLRFPRPVRVVS--GAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05852      1 PTFEFNPMKKKILAakGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGS---LEILNITKLDEGSYTCFAEN 76

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: 37.47 E-value: 6.04e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  260 GKHAKFRCYVMGKPEPEIEWHLEGRPLlPDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQTL 329
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHV-PDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRGMVF 69

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: 37.55 E-value: 6.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  139 VLRGEEVVLTCQVGGLPEPKLYWEKDGMAL-----DEVWDSSHFKLEPGRGASDEgasltlrilaarlpdsGVYVCHARN 213
Cdd:cd20958     12 AVAGQTLRLHCPVAGYPISSITWEKDGRRLplnhrQRVFPNGTLVIENVQRSSDE----------------GEYTCTARN 75

                           90
                   ....*....|....
gi 1883538138  214 AHGH-AQAGALLQV 226
Cdd:cd20958     76 QQGQsASRSVFVKV 89

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: 37.89 E-value: 6.17e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKfLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEK--DGMALDEVWDSSHFKLEPGRGASdegaSLTLRILaaRLPDSG 205
Cdd:cd05732      3 PK-ITYLENQTAVELEQITLTCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGHARVS----SLTLKDV--QLTDAG 75

                           90       100
                   ....*....|....*....|.
gi 1883538138  206 VYVCHARNAHGHAQAGALLQV 226
Cdd:cd05732     76 RYDCEASNRIGGDQQSMYLEV 96

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: 37.57 E-value: 6.23e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138  271 GKPEPEIEWHLEGRPLLpDRRRLMYRDRDGGFVLKVLYCQAKDRGLYVCAARNSAGQT 328
Cdd:cd05748     18 GRPTPTVTWSKDGQPLK-ETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEK 74

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: 37.23 E-value: 6.28e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138   26 GAEAELKCVVLGEPPPTVVWEKGGQQLVASERLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGT---LRISRVALHDQGQYECQAVN 61

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: 37.56 E-value: 6.42e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138 1007 VVLTCELSREDAP-VRWYKDGLEVEESEALVLQSDGPRRRLVLPAAQPEDGGEFVCDA 1063
Cdd:cd20972     19 VRLECRVTGNPTPvVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 37.51 E-value: 6.64e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138 1723 PREKTVLVNRRAVLEVTVSRPGGH-VCWMREGVELCPGNKYEMRRHGTthsLVIHDVRPEDQGTYSCQAGQD 1793
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHtVLWMKDGKPLGHSSRVQILSEDV---LVIPSVKREDKGMYQCFVRND 76

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: 37.56 E-value: 6.74e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1883538138  342 RFTRPLQDVEGREHGIVVLECKVPNSRIPTA-WFREDQRLLPCRKYEQIEEGAVRRLVIHKLKADDDGVYLC 412
Cdd:cd20972      3 QFIQKLRSQEVAEGSKVRLECRVTGNPTPVVrWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSC 74

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: 37.68 E-value: 6.81e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  241 PKPVLEPLKGApktfwVNEGKHAKFRCYVMGKPEPEIEWHLEGRPLLPDRRRLMYRDRDGGF---VLKVLYCQAKDRGLY 317
Cdd:cd20954      2 PRWIVEPVDAN-----VAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILpngTLVFGHVQKENEGHY 76

                           90       100
                   ....*....|....*....|
gi 1883538138  318 VCAARNSAGQTLSAV-QLHV 336
Cdd:cd20954     77 LCEAKNGIGSGLSKViFLKV 96

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: 37.60 E-value: 6.91e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1883538138   31 LKCVVLGEPPPTVVWEKGGQQL-VASERLSFPEDGAEhgLLLSGALPTDAGVYVCRARN 88
Cdd:cd05730     23 LACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSE--MTILDVDKLDEAEYTCIAEN 79

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: 37.86 E-value: 7.05e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  128 PKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKLYWEKDGMAldEVWDSSHFKLEPGRGASDEGASLTLRILAARlpDSGVY 207
Cdd:cd05734      2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGS--GVPQFQHIVPLNGRIQLLSNGSLLIKHVLEE--DSGYY 77


                   ....*....
gi 1883538138  208 VCHARNAHG 216
Cdd:cd05734     78 LCKVSNDVG 86

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 38.08 E-value: 7.50e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1722 PPREKTVLVNRRAVL--EVTVSRPGGHVCWMR-----------------EGVELCPGNKYEMRRHGTTH-SLVIHDVRPE 1781
Cdd:cd00099      4 SPRSLSVQEGESVTLscEVSSSFSSTYIYWYRqkpgqgpefliylssskGKTKGGVPGRFSGSRDGTSSfSLTISNLQPE 83

                           90
                   ....*....|....*...
gi 1883538138 1782 DQGTYSCQAGQDSADTQL 1799
Cdd:cd00099     84 DSGTYYCAVSESGGTDKL 101

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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: 409359 Cd Length: 102 Bit Score: 37.91 E-value: 7.71e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1883538138 1179 APNPLCVVPGEPVVLSCELSRASAQ--VF-WSHNGSPV--QQGEGLELRAEGPRRI--LCIQAADLAHTGVYTC 1245
Cdd:cd04970      8 APSNADITVGENATLQCHASHDPTLdlTFtWSFNGVPIdlEKIEGHYRRRYGKDSNgdLEIVNAQLKHAGRYTC 81

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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: 409359 Cd Length: 102 Bit Score: 37.91 E-value: 7.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138  127 APKFLTGPQSQWVLRGEEVVLTCQVGGLPEPKL--YWEKDGMALDEVWDSSHFKLEPGRGASDEgasltLRILAARLPDS 204
Cdd:cd04970      2 ATRITLAPSNADITVGENATLQCHASHDPTLDLtfTWSFNGVPIDLEKIEGHYRRRYGKDSNGD-----LEIVNAQLKHA 76

                           90       100
                   ....*....|....*....|....*
gi 1883538138  205 GVYVCHARNAHGHAQAGALLQVHQP 229
Cdd:cd04970     77 GRYTCTAQTVVDSDSASATLVVRGP 101

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 37.16 E-value: 8.00e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1883538138 1634 RSVSAREGDGATFECTVS---ETEITgrWELGGRALRPGGRVRIRQEGKKHILVLSELRTEDTGE 1695
Cdd:pfam13927    9 SSVTVREGETVTLTCEATgspPPTIT--WYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGT 71

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: 37.21 E-value: 9.47e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   31 LKCVVLGEPPPTVVWEKGGQQLvASERLSFPEDGAEHGLLLSGALPTDAGVYVCRARN 88
Cdd:cd05760     21 LRCHIDGHPRPTYQWFRDGTPL-SDGQGNYSVSSKERTLTLRSAGPDDSGLYYCCAHN 77

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: 9.47e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1883538138   17 FPRPVRVVSGAEA---ELKCVVLGEPPPTVVWEKGGQQLVASE---RLSFPEDGAehgLLLSGALPTDAGVYVCRARN 88
Cdd:cd20969      5 RDRKAQQVFVDEGhtvQFVCRADGDPPPAILWLSPRKHLVSAKsngRLTVFPDGT---LEVRYAQVQDNGTYLCIAAN 79

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: 37.09 E-value: 9.55e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1883538138 1539 IVQGPQDLEVTEGDTATFECELSQTLADVI-WEKDG-QALSLSPRLRLQALGTRRLLLLRRccsSDAGTYSCV 1609
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTIsWLKDGvPLLGKDERITTLENGSLQIKGAEK---SDTGEYTCV 71

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: 37.16 E-value: 9.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1883538138 1359 FLRRLQDVRAEEGQDVHLevetgRVGAAG----TVRWIRGGEPLPLDSRLTTAQDGhvhRLSIHGV-LLTDQGTYGCESR 1433
Cdd:cd20958      3 FIRPMGNLTAVAGQTLRL-----HCPVAGypisSITWEKDGRRLPLNHRQRVFPNG---TLVIENVqRSSDEGEYTCTAR 74