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 1842190479 439 GPPIISSEAVQFAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 518
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1842190479 519 NCTAWNSFGPGTAIIQLE 536
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 340 PRIVVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKDSNMgprlpgsPPEANLSAQVLSNSQQLLLKSVTQADAGIYTC 419
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI-------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1842190479 420 RA 421
Cdd:pfam13927  75 VA 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1842190479 254 PPTVTLSIEPQTVLEGERVVFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT 314
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLT 60

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 1842190479 439 GPPIISSEAVQFAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 518
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1842190479 519 NCTAWNSFGPGTAIIQLE 536
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 340 PRIVVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKDSNMgprlpgsPPEANLSAQVLSNSQQLLLKSVTQADAGIYTC 419
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI-------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1842190479 420 RA 421
Cdd:pfam13927  75 VA 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 1842190479  346 PKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmGPRLPGSPPEANLSAQvlSNSQQLLLKSVTQADAGIYTCRAiVPR 425
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQ----GGKLLAESGRFSVSRS--GSTSTLTISNVTPEDSGTYTCAA-TNS 73

                           90
                   ....*....|..
gi 1842190479  426 IGVAEREVPLYV 437
Cdd:smart00410  74 SGSASSGTTLTV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 157 IDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTVSQLLIQPTDLDIGRVFTCRSMN 236
Cdd:pfam08205   3 IEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSY 82

                  ..
gi 1842190479 237 EA 238
Cdd:pfam08205  83 GA 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1842190479 254 PPTVTLSIEPQTVLEGERVVFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT 314
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLT 60

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479  451 AVRGDGGKVECFIgSTPPPDRIAWaWKENFLEVGTLERYTVertnSGSGVLSTLTINNVMEADFQThYNCTAWNSFGPGT 530
Cdd:smart00410   6 VKEGESVTLSCEA-SGSPPPEVTW-YKQGGKLLAESGRFSV----SRSGSTSTLTISNVTPEDSGT-YTCAATNSSGSAS 78

                   ....*.
gi 1842190479  531 AIIQLE 536
Cdd:smart00410  79 SGTTLT 84

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1842190479 259 LSIEPQ--TVLEGERVVFTCQATANPEILGYRWAKGGFLIEDAHES 302
Cdd:cd05752     3 VSLDPPwtTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTSSS 48

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 1842190479 439 GPPIISSEAVQFAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 518
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1842190479 519 NCTAWNSFGPGTAIIQLE 536
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; 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 (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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 439 GPPIISSEAVQFAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 518
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1842190479 519 NCTAWNSFGPGTAIIQLE 536
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 340 PRIVVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKDSNMgprlpgsPPEANLSAQVLSNSQQLLLKSVTQADAGIYTC 419
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL-------RSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73

                  ..
gi 1842190479 420 RA 421
Cdd:pfam07679  74 VA 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479  346 PKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmGPRLPGSPPEANLSAQvlSNSQQLLLKSVTQADAGIYTCRAiVPR 425
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQ----GGKLLAESGRFSVSRS--GSTSTLTISNVTPEDSGTYTCAA-TNS 73

                           90
                   ....*....|..
gi 1842190479  426 IGVAEREVPLYV 437
Cdd:smart00410  74 SGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479  54 RFSQEPADQTVVAGQRAVLPCvllNYSG----IVQWTKDGlalgmgQGLKAWPRYRVvgSADAGQYNLEITDAELSDDAS 129
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTC---TVTGtpdpEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                          90       100
                  ....*....|....*....|
gi 1842190479 130 YECQAT-EAALRSRRAKLTV 148
Cdd:pfam07679  71 YTCVATnSAGEAEASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 157 IDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTVSQLLIQPTDLDIGRVFTCRSMN 236
Cdd:pfam08205   3 IEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSY 82

                  ..
gi 1842190479 237 EA 238
Cdd:pfam08205  83 GA 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 340 PRI-VVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKDsnmgprlpGSPPeanlSAQVLSNSQQLL-LKSVTQADAGIY 417
Cdd:cd04968     1 PSIkVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVD--------GSPS----SQWEITTSEPVLeIPNVQFEDEGTY 68

                  ....
gi 1842190479 418 TCRA 421
Cdd:cd04968    69 ECEA 72

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 1842190479 149 LIPPEDTRIDggpvILLQA--GTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTEllkDGKRETTVSQLLIQPTDLDI 226
Cdd:cd05885     1 LVAPENPVVE----VREQAveGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRVDRKDD 73

                          90       100
                  ....*....|....*....|....*..
gi 1842190479 227 GRVFTCRSMNEAIPNG--KETSIELDV 251
Cdd:cd05885    74 GGIVICEAQNQALPSGhsKQTQYVLDV 100

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 161 PVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQqegaVTSTELLKDGKRETTVSQLLIQPTDLDIGRVFTCRSMNEAIP 240
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGT----LIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79

                  ....*..
gi 1842190479 241 NGKETSI 247
Cdd:pfam00047  80 ATLSTSL 86

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479  57 QEPADQTVVAGQRAVLPCvllnyS---GI----VQWTKDGLALGMGQglkawPRYRVVGSAdagqyNLEITDAELSDDAS 129
Cdd:cd05724     2 VEPSDTQVAVGEMAVLEC-----SpprGHpeptVSWRKDGQPLNLDN-----ERVRIVDDG-----NLLIAEARKSDEGT 66

                          90       100
                  ....*....|....*....|.
gi 1842190479 130 YECQAT--EAALRSRRAKLTV 148
Cdd:cd05724    67 YKCVATnmVGERESRAARLSV 87

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 340 PRIVVYPKPTTTDI--GSDVTLTCVWAGNPPLTLTWTKKDsnmgprlpGSPPEANLSAQVLSNSQQLLLKSVTQADAGIY 417
Cdd:cd20970     1 PVISTPQPSFTVTAreGENATFMCRAEGSPEPEISWTRNG--------NLIIEFNTRYIVRENGTTLTIRNIRRSDMGIY 72

                          90       100
                  ....*....|....*....|
gi 1842190479 418 TCRAIVPRIGVAEREVPLYV 437
Cdd:cd20970    73 LCIASNGVPGSVEKRITLQV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 343 VVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKDSNmGPRLPGSPPEANlSAQVLSNSQQLLLKSVTQADAGIYTCRAI 422
Cdd:cd05726     3 VVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQ-NLLFPYQPPQPS-SRFSVSPTGDLTITNVQRSDVGYYICQAL 80

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 346 PKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmGPRLPGSPPEANLSaqvlSNSqqLLLKSVTQADAGIYTCRAiVPR 425
Cdd:cd20978     8 EKNVVVKGGQDVTLPCQVTGVPQPKITWLHN----GKPLQGPMERATVE----DGT--LTIINVQPEDTGYYGCVA-TNE 76

                          90
                  ....*....|..
gi 1842190479 426 IGVAEREVPLYV 437
Cdd:cd20978    77 IGDIYTETLLHV 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842190479 255 PTVTLSIEPQTVLEGERVVFTCQATAN--PEIlgyRWAKGGFLIEDAHESRY-ETNVDYSFFTEPV--------SCEVYN 323
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTpdPEV---SWFKDGQPLRSSDRFKVtYEGGTYTLTISNVqpddsgkyTCVATN 77

                          90
                  ....*....|...
gi 1842190479 324 KVGSTNVSTLVNV 336
Cdd:pfam07679  78 SAGEAEASAELTV 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.

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gi 1842190479 353 IGSDVTLTCVWAGNPPLTLTWTKKDSNMGPRLPGSPPEANLSaqvlsnsqqLLLKSVTQADAGIYTCR 420
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWT---------LSLKNLKPEDSGKYTCH 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.

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gi 1842190479 344 VYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmgprlpGSPPEANLSAQVLSNSqQLLLKSVTQADAGIYTC 419
Cdd:cd20957     6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKD---------GKPLGHSSRVQILSED-VLVIPSVKREDKGMYQC 71

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

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gi 1842190479 148 VLIPPEDTRIDGGPVillqagtpyNLTCRAFNAKPA-ATIIWFRDGTQQEGAV--TSTELLKDGKRETTvSQLLIQPTDL 224
Cdd:cd00098     3 TLLPPSPEEKGGGKV---------TLVCLVSGFYPKdITVTWLKNGVPLTSGVstSSPVEPNDGTYSVT-SSLTVPPSDW 72

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gi 1842190479 225 DIGRVFTCR 233
Cdd:cd00098    73 DEGATYTCV 81

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

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gi 1842190479 341 RIVVYPKPTTTdIGSDVTLTCVWAGNPPLTLT---WTKKDSN-----------MGPRLPGSPPE--ANLSAQVLSNSQQL 404
Cdd:cd05718     2 RVQVPTEVTGF-LGGSVTLPCSLTSPGTTKITqvtWMKIGAGssqnvavfhpqYGPSVPNPYAErvEFLAARLGLRNATL 80

                          90
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gi 1842190479 405 LLKSVTQADAGIYTC 419
Cdd:cd05718    81 RIRNLRVEDEGNYIC 95

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.

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gi 1842190479 340 PRIVVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmGPRLPGSPPEANLSAQVLSNSQQLLLKSV----TQADAG 415
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKN----GQPLETDKDDPRSHRIVLPSGSLFFLRVVhgrkGRSDEG 76

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gi 1842190479 416 IYTCRA 421
Cdd:cd07693    77 VYVCVA 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

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gi 1842190479 342 IVVYPKPTTTDIGSDVTLTCVWAGNPPLTLTWTKKdsnmGPRLPGSPPEANLsaqvLSNSqQLLLKSVTQADAGIYTCRA 421
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKD----GVPLLGKDERITT----LENG-SLQIKGAEKSDTGEYTCVA 72

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.

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gi 1842190479 346 PKPTTTDIGSDVTLTC-VWAGNPPLTLTWTKKDSnmgpRLPGSPPEANLSAQVLSNSqqLLLKSVTQADAGIYTCRAIVP 424
Cdd:pfam00047   3 PPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGG----TLIESLKVKHDNGRTTQSS--LLISNVTKEDAGTYTCVVNNP 76

                          90
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gi 1842190479 425 rIGVAEREVPL 435
Cdd:pfam00047  77 -GGSATLSTSL 86

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

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gi 1842190479 173 LTCRAFNAKPA-ATIIWFRDGT--QQEGAVTSTELLKDGKRETTVSQLLIQPTDLDIGRVFTCRSMNEAIPN 241
Cdd:cd05768    21 LTCLVKGFYPEdIFVSWLQNGEplPSADYKTTAPVPESDGSFFVYSKLNVSTADWNSGDVFSCVVGHEALPL 92

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

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gi 1842190479 488 RYTVERTNSGSGVLSTLTINNVMEADfQTHYNCTAWNSFGPGTAIIQLEERE 539
Cdd:cd05735    51 RYLVTTKEVGDEVISTLQILPTVRED-SGFFSCHAINSYGEDRGIIQLTVQE 101