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 1348572393 329 GPPTISSTQTHQALHGEKGEIKCFIRSTPPPDRIV--SNTNTTSFNIYLFYLSLLATALHGIWVALQPWCPDRAPVAlSA 406
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAwaWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQ-TH 79

                          90
                  ....*....|....*....
gi 1348572393 407 FNCTAWNSFGSDTEIIRLK 425
Cdd:cd05898    80 YNCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 165 LSVEPQPILEGNLVKFHCSAKANPPVTlYRWAKGGNVIKEvSGD--TYEVIVDHS-FFTepvsCEVTNPLGSTnISRNVD 241
Cdd:pfam13895   4 LTPSPTVVTEGEPVTLTCSAPGNPPPS-YTWYKDGSAISS-SPNffTLSVSAEDSgTYT----CVARNGRGGK-VSNPVE 76

                  .
gi 1348572393 242 V 242
Cdd:pfam13895  77 L 77

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 329 GPPTISSTQTHQALHGEKGEIKCFIRSTPPPDRIV--SNTNTTSFNIYLFYLSLLATALHGIWVALQPWCPDRAPVAlSA 406
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAwaWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQ-TH 79

                          90
                  ....*....|....*....
gi 1348572393 407 FNCTAWNSFGSDTEIIRLK 425
Cdd:cd05898    80 YNCTAWNSFGSGTAIIQLE 98

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1348572393 252 PQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRG------SGVVLSNENILTLKAVRQEDAGKYVC 309
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1348572393  66 GPVVSLRAGDP-LNLTCHADNAKPAASIIWIRNGEVLNGAMYSKTLLRDGRRESTVSTLYLSASNIETGQQIICRASN 142
Cdd:pfam08205   5 PPASLLEGEGPeVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSY 82

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 169 PQPILEGNlVKFHCSAKANPPVTlYRWAKGGNVIKEVSGDTYEVIVDHSFFTEPVS--------CEVTNPLGsTNISRNV 240
Cdd:cd05850    15 PEGSAEEK-VTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-TVVSREA 91

                  ....*
gi 1348572393 241 DVYFG 245
Cdd:cd05850    92 SLRFG 96

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 329 GPPTISSTQTHQALHGEKGEIKCFIRSTPPPDRIV--SNTNTTSFNIYLFYLSLLATALHGIWVALQPWCPDRAPVAlSA 406
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAwaWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQ-TH 79

                          90
                  ....*....|....*....
gi 1348572393 407 FNCTAWNSFGSDTEIIRLK 425
Cdd:cd05898    80 YNCTAWNSFGSGTAIIQLE 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGS-------GVVLSNENI--LTLKAVRQEDAGKYVCRAVVPrV 316
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGTytLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 1348572393 317 GAGEKEVSLTV 327
Cdd:pfam07679  80 GEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRG---------SGVVLSNENILTLKAVRQEDAGKYVCRA 311
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393  252 PQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENI----------LTLKAVRQEDAGKYVCRAvVPRVGAGEK 321
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 1348572393  322 EVSLTV 327
Cdd:smart00410  80 GTTLTV 85

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 251 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENILTL-------KAVRQEDAGKYVCravVPRVGAGEKEV 323
Cdd:cd20952     5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLengslqiKGAEKSDTGEYTC---VALNLSGEATW 81

                  ....
gi 1348572393 324 SLTV 327
Cdd:cd20952    82 SAVL 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 263 AVFNCAWTGNPSLTIVWMKRGSGV---------VLSNENILTLKAVRQEDAGKYVCRAVVPRVGAGEKEV 323
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLppssrdsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393  55 LVPPEDPVIRggpvVSLRA--GDPLNLTCHADNAKPAASIIWIRNGEVLNGAMYSKtllRDGRRESTVSTLYLSASNIET 132
Cdd:cd05885     1 LVAPENPVVE----VREQAveGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQ---ENGKVWSVASTVRFRVDRKDD 73

                          90       100
                  ....*....|....*....|....*..
gi 1348572393 133 GQQIICRASNKAVPNG--KETSVNIDI 157
Cdd:cd05885    74 GGIVICEAQNQALPSGhsKQTQYVLDV 100

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1348572393 251 EPQSLQVDLGSDAVFNC-AWTGNPSLTIVWmKRGSGVVLSNE----NILTLKAVRQEDAGKYVC 309
Cdd:cd05754     7 EPRSQEVRPGADVSFICrAKSKSPAYTLVW-TRVNGTLPSRAmdfnGILTIRNVQLSDAGTYVC 69

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1348572393 251 EPQSLQVDLGSDAVFNC-AWTGNPSLTIVWMKRGSGVVLSNENI-------LTLKAVRQEDAGKYVCRA 311
Cdd:cd05724     3 EPSDTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNERVrivddgnLLIAEARKSDEGTYKCVA 71

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 251 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLS-----NENILTLKAVRQEDAGKYVCRAvVPRVGAGEKEVSL 325
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA-ENMVGKIEASATL 81

                  ..
gi 1348572393 326 TV 327
Cdd:cd05725    82 TV 83

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 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENI--------LTLKAVRQEDAGKYVCRAvVPRVG 317
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRStceagvgeLHIQDVLPEDHGTYTCLA-KNAAG 80

                          90
                  ....*....|
gi 1348572393 318 AGEKEVSLTV 327
Cdd:cd20976    81 QVSCSAWVTV 90

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1348572393 259 LGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNEN-------ILTLKAVRQEDAGKYVCRaVVPRVGA 318
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGenkkkkwTLSLKNLKPEDSGKYTCH-VSNRAGE 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 247 RMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENILT---------LKAVRQEDAGKYvcrAVVPRVG 317
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITsteykstfeISKVQMSDEGNY---TVVVENS 81

                          90
                  ....*....|
gi 1348572393 318 AGEKEVSLTV 327
Cdd:cd05747    82 EGKQEAQFTL 91

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVW-MKRGSGV--------------VLSNENILtLKAVRQEDAGKYVCR 310
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkHSKGSGVpqfqhivplngriqLLSNGSLL-IKHVLEEDSGYYLCK 80

                  .
gi 1348572393 311 A 311
Cdd:cd05734    81 V 81

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 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGV-------VLSNEN---ILTLKAVRQEDAGKYVCRAvvpR 315
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpdsahkMLVRENgrhSLIIEPVTKRDAGIYTCIA---R 77

                          90
                  ....*....|...
gi 1348572393 316 VGAGEKEVSLTVN 328
Cdd:cd05744    78 NRAGENSFNAELV 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1348572393 251 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNEN--------ILTLKAVRQEDAGKYVCRA 311
Cdd:cd04978     5 EPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDmrrtvdgrTLIFSNLQPNDTAVYQCNA 73

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393  67 PVVSLRAGDPL-----NLT----CHADNAKPAASIIWirNGEVlnGAMYSKTLLRDGRRESTVSTLYLSASNIETGQQII 137
Cdd:cd07704     1 PLVSLNPGPALlidggNETlaasCTAETGKPAASVTW--ETDL--GGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLT 76

                          90       100
                  ....*....|....*....|
gi 1348572393 138 CRASNKAVPNGKETSVNIDI 157
Cdd:cd07704    77 CVVSHPALQQDIRITHILDV 96

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1348572393 251 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSN------ENILTLKAVRQEDAGKYVCRA 311
Cdd:cd05723     3 KPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDyfkivkEHNLQVLGLVKSDEGFYQCIA 69

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1348572393 247 RMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLS---------NENILTLKAVRQEDAGKYVCRA 311
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmskyriLADGLLINKVTQDDTGEYTCRA 74

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 175 GNLVKFHCSAKANPPVTLyRWAKGGNVIKE---VSGdtYEVIVDH-SFFTEPV--------SCEVTNPLGSTNISRNVDV 242
Cdd:cd05857    19 ANTVKFRCPAAGNPTPTM-RWLKNGKEFKQehrIGG--YKVRNQHwSLIMESVvpsdkgnyTCVVENEYGSINHTYHLDV 95

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1348572393 169 PQPILEGNlVKFHCSAKANPPVTlYRWAKGGNVIKEVSGDTYEVIVDHSFFTEPVS--------CEVTNPLGSTnISRNV 240
Cdd:cd04967    14 PEDSDEKK-VALNCRARANPVPS-YRWLMNGTEIDLESDYRYSLVDGTLVISNPSKakdaghyqCLATNTVGSV-LSREA 90

                  ....*
gi 1348572393 241 DVYFG 245
Cdd:cd04967    91 TLQFG 95

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1348572393  77 LNLTCHAdNAKPAASIIWIRNGEVLNGAMYSktllrDGRRESTVSTLYLSASNIETGQQIICRASNKA 144
Cdd:cd00096     1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRD-----SRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1348572393 246 PRMSAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGV---------VLSNENILTLKAVRQEDAGKYVCRA 311
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDInpklskqltLIANGSELHISNVRYEDTGAYTCIA 75