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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000  164 GAQVGLSCEVRAVPTPVITWRKvmqspeGTQALEelPGDHVNIAVQvrggpsdhEATAWILINPLRKEDEGVYQCHAANM 243
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFK------DGQPLR--SSDRFKVTYE--------GGTYTLTISNVQPDDSGKYTCVATNS 78

                          90
                  ....*....|..
gi 966992000  244 VGEAESHSTVTV 255
Cdd:pfam07679  79 AGEAEASAELTV 90

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 966992000   109 VCGSDGRSYPSVCALRLRARHKPRahpgHLHKARDGPC 146
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGK----SIEVKHDGPC 46

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000  164 GAQVGLSCEVRAVPTPVITWRKvmqspeGTQALEelPGDHVNIAVQvrggpsdhEATAWILINPLRKEDEGVYQCHAANM 243
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFK------DGQPLR--SSDRFKVTYE--------GGTYTLTISNVQPDDSGKYTCVATNS 78

                          90
                  ....*....|..
gi 966992000  244 VGEAESHSTVTV 255
Cdd:pfam07679  79 AGEAEASAELTV 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 169 LSCEVRAVPTPVITWRKvmqspegtqaleelpgDHVNIAVQVRGGPSDHEATAWILINPLRKEDEGVYQCHAANMVGEAE 248
Cdd:cd00096    3 LTCSASGNPPPTITWYK----------------NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

                 ....
gi 966992000 249 SHST 252
Cdd:cd00096   67 SASV 70

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 966992000   109 VCGSDGRSYPSVCALRLRARHKPRahpgHLHKARDGPC 146
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGK----SIEVKHDGPC 46

Insulin growth factor-binding protein homologues; High affinity binding partners of insulin-like growth factors.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 966992000    53 SARDECGCCSRCLGAEGASCGGRAGaRCGPGLVC-----ASRAAGAAPEGTGLCV 102
Cdd:smart00121  22 VRLDGCGCCPVCARQEGEPCGVYTP-RCAPGLRCqpppgEERPLRALLHGQGVCM 75

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000  164 GAQVGLSCEVRAVPTPVITWRKvmqspeGTQALEelPGDHVNIAVQvrggpsdhEATAWILINPLRKEDEGVYQCHAANM 243
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFK------DGQPLR--SSDRFKVTYE--------GGTYTLTISNVQPDDSGKYTCVATNS 78

                          90
                  ....*....|..
gi 966992000  244 VGEAESHSTVTV 255
Cdd:pfam07679  79 AGEAEASAELTV 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 169 LSCEVRAVPTPVITWRKvmqspegtqaleelpgDHVNIAVQVRGGPSDHEATAWILINPLRKEDEGVYQCHAANMVGEAE 248
Cdd:cd00096    3 LTCSASGNPPPTITWYK----------------NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

                 ....
gi 966992000 249 SHST 252
Cdd:cd00096   67 SASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000  157 RSVHNVTGAQVGLSCEVRAVPTPVITWRKvmqspegtqaleelPGDHVNIAVQVRGGPSDHEATawILINPLRKEDEGVY 236
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITWYK--------------NGEPISSGSTRSRSLSGSNST--LTISNVTRSDAGTY 72

                  ....*.
gi 966992000  237 QCHAAN 242
Cdd:pfam13927  73 TCVASN 78

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWrkvmqSPEGtQALEELP----GDHVNiavqvrggpSDHEATAWILINPLRKEDEGVYQCH 239
Cdd:cd20956   16 GPSVSLKCVASGNPLPQITW-----TLDG-FPIPESPrfrvGDYVT---------SDGDVVSYVNISSVRVEDGGEYTCT 80

                         90
                 ....*....|..
gi 966992000 240 AANMVGEAeSHS 251
Cdd:cd20956   81 ATNDVGSV-SHS 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 159 VHNVTGAQVG----LSCEVRAVPTPVITWRKvmqspeGTQALEELPgdhvNIAVQVRGGpsdheatawILINPLRKEDEG 234
Cdd:cd04969    8 VKKKILAAKGgdviIECKPKASPKPTISWSK------GTELLTNSS----RICILPDGS---------LKIKNVTKSDEG 68

                         90       100
                 ....*....|....*....|.
gi 966992000 235 VYQCHAANMVGEAESHSTVTV 255
Cdd:cd04969   69 KYTCFAVNFFGKANSTGSLSV 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 160 HNVT-GAQVGLSCEVRAVPTPVITWRKvmqspegtqALEELPGDHVNIavqvRGGPSDH-EATAWILINPLRKEDEGVYQ 237
Cdd:cd20954   11 ANVAaGQDVMLHCQADGFPTPTVTWKK---------ATGSTPGEYKDL----LYDPNVRiLPNGTLVFGHVQKENEGHYL 77

                 ....*...
gi 966992000 238 CHAANMVG 245
Cdd:cd20954   78 CEAKNGIG 85

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 157 RSVHNVTGAQVGLSCEVRAVPTPVITWRKVmqspegtqaLEELPGdhvNIAVQVRGgpsdheatAWILINPLRKEDEGVY 236
Cdd:cd05851    9 KDTYALKGQNVTLECFALGNPVPVIRWRKI---------LEPMPA---TAEISMSG--------AVLKIFNIQPEDEGTY 68

                         90
                 ....*....|....*....
gi 966992000 237 QCHAANMVGEAESHSTVTV 255
Cdd:cd05851   69 ECEAENIKGKDKHQARVYV 87

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000  157 RSVHNVTGAQVGLSCEVR---AVPTPVITWRKVMQSPEGTQAL-EELPGDHVNI---AVQVRGGPSDHEATawILINPLR 229
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSssmSEASTSVYWYRQPPGKGPTFLIaYYSNGSEEGVkkgRFSGRGDPSNGDGS--LTIQNLT 81

                          90       100
                  ....*....|....*....|....*...
gi 966992000  230 KEDEGVYQCHAANMVGEAESHST-VTVL 256
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEGVFGKGTrLTVL 109

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 966992000   109 VCGSDGRSYPSVCALRLRARHKPRahpgHLHKARDGPC 146
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGK----SIEVKHDGPC 46

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 158 SVHNVTGAQVGLSCEVRAVPTPVITWRKVMQSPEG--TQALEELPGDHVNIAVQVrggpSDHeATAWILINPLRKEDEGV 235
Cdd:cd20940    9 SQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEicSQLWDGARLDRVHINATY----HQH-ATSTISIDNLTEEDTGT 83

                 ....*..
gi 966992000 236 YQCHAAN 242
Cdd:cd20940   84 YECRASN 90

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 162 VTGAQVGLSCEVRAVPTPVITWRKVMQSPEgtqaleeLPGDHVNIAVQVrggpsdheatAWILINPLRKEDEGVYQCHAA 241
Cdd:cd20976   14 VEGQDFVAQCSARGKPVPRITWIRNAQPLQ-------YAADRSTCEAGV----------GELHIQDVLPEDHGTYTCLAK 76

                         90
                 ....*....|....
gi 966992000 242 NMVGEAESHSTVTV 255
Cdd:cd20976   77 NAAGQVSCSAWVTV 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWR---KVMQspegtqaleelPGDHVNIAVQVRGGPSdheatawILINPLRKEDEGVYQCHA 240
Cdd:cd05744   15 GRLCRFDCKVSGLPTPDLFWQlngKPVR-----------PDSAHKMLVRENGRHS-------LIIEPVTKRDAGIYTCIA 76

                 ....*...
gi 966992000 241 ANMVGEAE 248
Cdd:cd05744   77 RNRAGENS 84

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 157 RSVHNVTGAQVGLSCEVRAVPTPVITWRKvmqspEGTQaLEELPGdhvniaVQVRGGPSDHEatawILINPLRKEDEGVY 236
Cdd:cd20972    9 RSQEVAEGSKVRLECRVTGNPTPVVRWFC-----EGKE-LQNSPD------IQIHQEGDLHS----LIIAEAFEEDTGRY 72

                         90
                 ....*....|....*....
gi 966992000 237 QCHAANMVGEAESHSTVTV 255
Cdd:cd20972   73 SCLATNSVGSDTTSAEIFV 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 159 VHNVT---GAQVGLSCEVRAVPTPVITWRKvmqSPEGTQALEELPGDHvniaVQVRGgpsdHEATAWILINPLRKEDEGV 235
Cdd:cd05732    8 LENQTaveLEQITLTCEAEGDPIPEITWRR---ATRGISFEEGDLDGR----IVVRG----HARVSSLTLKDVQLTDAGR 76

                         90
                 ....*....|
gi 966992000 236 YQCHAANMVG 245
Cdd:cd05732   77 YDCEASNRIG 86

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 966992000 109 VCGSDGRSYPSVCALRLRARHKPRahpgHLHKARDGPC 146
Cdd:cd00104    8 VCGSDGKTYSNECHLGCAACRSGR----SITVAHNGPC 41

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWRKvmqspegtqaleelpgDHVNIAVQVRGGPSDHEATAWILI-NPLRKEDEGVYQCHAAN 242
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLK----------------DGKEFKKEHRIGGTKVEEKGWSLIiERAIPRDKGKYTCIVEN 82

                         90
                 ....*....|...
gi 966992000 243 MVGEAESHSTVTV 255
Cdd:cd05729   83 EYGSINHTYDVDV 95

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 163 TGAQVGLSCEVRAVPTPVITWRKvmqspEGtqaleelpGDHVNIAVQVRGG--PSDHEatawILINPLRKEDEGVYQCHA 240
Cdd:cd05763   13 AGSTARLECAATGHPTPQIAWQK-----DG--------GTDFPAARERRMHvmPEDDV----FFIVDVKIEDTGVYSCTA 75

                         90
                 ....*....|....*.
gi 966992000 241 ANMVGEAESHSTVTVL 256
Cdd:cd05763   76 QNSAGSISANATLTVL 91

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWRKvmqspeGTQALeeLPGDHVNIavqvrggpsdheataW----ILINPLRKEDEGVYQCH 239
Cdd:cd05852   17 GGRVIIECKPKAAPKPKFSWSK------GTELL--VNNSRISI---------------WddgsLEILNITKLDEGSYTCF 73

                         90
                 ....*....|....*.
gi 966992000 240 AANMVGEAESHSTVTV 255
Cdd:cd05852   74 AENNRGKANSTGVLSV 89

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 162 VTGAQVGLSCEVRAVPTPVITWRKVMQ------SPEGTQALEELPGDHVNIavqvrggpSDHEATAWILINpLRKEDEGV 235
Cdd:cd05858   14 VVGTDAEFVCKVYSDAQPHIQWLKHVEkngskyGPDGLPYVEVLKTAGVNT--------TDKEIEVLYLRN-VTFEDAGE 84

                         90       100
                 ....*....|....*....|.
gi 966992000 236 YQCHAANMVGEAESHSTVTVL 256
Cdd:cd05858   85 YTCLAGNSIGISHHSAWLTVL 105

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWRKvmqspeGTQALEELpgDHVNiaVQVRGGpsdheATAWILINPLRKEDEGVYQCHAANM 243
Cdd:cd05737   16 GKTLNLTCNVWGDPPPEVSWLK------NDQALAFL--DHCN--LKVEAG-----RTVYFTINGVSSEDSGKYGLVVKNK 80

                         90
                 ....*....|..
gi 966992000 244 VGEAESHSTVTV 255
Cdd:cd05737   81 YGSETSDVTVSV 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966992000 164 GAQVGLSCEVRAVPTPVITWRKvmqspEGTQAL---EELPGDHVNIAVQVRGGpsdheatawILINPLRKEDEGVYQCHA 240
Cdd:cd05726   14 GRTVTFQCETKGNPQPAIFWQK-----EGSQNLlfpYQPPQPSSRFSVSPTGD---------LTITNVQRSDVGYYICQA 79

                         90
                 ....*....|....*....
gi 966992000 241 ANMVGEAESHSTVTVLDLS 259
Cdd:cd05726   80 LNVAGSILAKAQLEVTDVL 98