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 1487364445 330 GPPIISSDSIQYAVRGDRGKVECFIGSTPLPDRIAWGWKEKTLETGTLERYTVERSNTEDGVLSTLTINNVMEVDFQTRY 409
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1487364445 410 NCTAWNAFGPRTAIIQLE 427
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1487364445 247 PRIVMDPKPLITDIGSDVTLTCVWTGNPPLTLTWAK---------KESNMILGNSNQLHLKSVTQSDAGLYVCKA 312
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepissgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1487364445   12 RITGVTDSGQFNLEITDAELSDDALYECQAT-EAALRSRRAKLNV 55
Cdd:smart00410  41 RFSVSRSGSTSTLTISNVTPEDSGTYTCAATnSSGSASSGTTLTV 85

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 1487364445 330 GPPIISSDSIQYAVRGDRGKVECFIGSTPLPDRIAWGWKEKTLETGTLERYTVERSNTEDGVLSTLTINNVMEVDFQTRY 409
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1487364445 410 NCTAWNAFGPRTAIIQLE 427
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1487364445 247 PRIVMDPKPLITDIGSDVTLTCVWTGNPPLTLTWAK---------KESNMILGNSNQLHLKSVTQSDAGLYVCKA 312
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepissgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 264 VTLTCVWTGNPPLTLTWAK---------KESNMILGNSNQLHLKSVTQSDAGLYVCKAIVPRIGVGEREV 324
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKngkplppssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1487364445 161 PPTVTLSIQPQTVQEGERVTFTCLANANPEIKgYRWAKGGTIIEDAKESKYETQVDYTFFT-EPVS--------CEVRN 230
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLTiSNVTrsdagtytCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445  169 QPQTVQEGERVTFTCLANANPEIKGY-RWAKGGTIIEDAKESKYETQVDYTFFTEPVS--------CEVRNDVGSTNVSI 239
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTwYKQGGKLLAESGRFSVSRSGSTSTLTISNVTpedsgtytCAATNSSGSASSGT 81

                   ....
gi 1487364445  240 LVDV 243
Cdd:smart00410  82 TLTV 85

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1487364445   12 RITGVTDSGQFNLEITDAELSDDALYECQAT-EAALRSRRAKLNV 55
Cdd:smart00410  41 RFSVSRSGSTSTLTISNVTPEDSGTYTCAATnSSGSASSGTTLTV 85

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 1487364445 330 GPPIISSDSIQYAVRGDRGKVECFIGSTPLPDRIAWGWKEKTLETGTLERYTVERSNTEDGVLSTLTINNVMEVDFQTRY 409
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1487364445 410 NCTAWNAFGPRTAIIQLE 427
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 1487364445 330 GPPIISSDSIQYAVRGDRGKVECFIGSTPLPDRIAWGWKEKTLETGTLERYTVERSNTEDGVLSTLTINNVMEVDFQTRY 409
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1487364445 410 NCTAWNAFGPRTAIIQLE 427
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. 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 1487364445  56 LIPPEDPMIDGAPEILLRAGTPhNLTCRAQNAKPAATIIWFRDglpQSEAATATEVLMDGKRKT-TI-SQLLITPTDLDI 133
Cdd:cd05761     1 LGVPEKPVITGFTSPVVEGDEI-TLTCTTSGSKPAADIRWFKN---DKELKGVKEVQESGAGKTfTVtSTLRFRVDRDDD 76

                          90       100
                  ....*....|....*....|....*.
gi 1487364445 134 GRVYVCRCSNEAIPAG-KEASIKLNV 158
Cdd:cd05761    77 GVAVICRVDHESLTSTpKQTQQVLEV 102

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 1487364445 264 VTLTCVWTGNPPLTLTWAK---------KESNMILGNSNQLHLKSVTQSDAGLYVCKAIVPRIGVGEREV 324
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKngkplppssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445  253 PKPLITDIGSDVTLTCVWTGNPPLTLTWAKKESNMIL----------GNSNQLHLKSVTQSDAGLYVCKAiVPRIGVGER 322
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAesgrfsvsrsGSTSTLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 1487364445  323 EVALLV 328
Cdd:smart00410  80 GTTLTV 85

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 1487364445 251 MDPKPLITDIGSDVTLTCVWTGNPPLTLTWAK------KESNMILGNSNQLHLKSVTQSDAGLYVC 310
Cdd:cd20957     6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKdgkplgHSSRVQILSEDVLVIPSVKREDKGMYQC 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1487364445 253 PKPLITDIGSDVTLTCVWTGNPPLTLTWAKKESNMILGNSNQLHLKS-----VTQSDAGLYVCKA 312
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHSlkirkVTAGDMGSYTCVA 68

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); 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 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445  56 LIPPEDPMIDGAPEILLRaGTPHNLTCRAQNAKPAATIIWFRDglpQSEAATATEV-LMDGKRKTTISQLLITPTDLDIG 134
Cdd:cd05883     1 LVPPRNLVIDIQKDTAVE-GEEIELNCTAMASKPAATIRWFKG---NKELTGKSEVeEWYSRMFTVTSQLMLKVTKEDDG 76

                          90
                  ....*....|..
gi 1487364445 135 RVYVCRCSNEAI 146
Cdd:cd05883    77 VPVICLVDHPAV 88

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 247 PRIVMDPKPLITDIGSDVTLTCVWTGNPPLTLTWAK----KE----------SNMILGNSNQLHLKSVTQSDAGLYVCKA 312
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvpgKEnlimrpnhvrGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80

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 1487364445  56 LIPPEDPMIDGAPEILlrAGTPHNLTCRAQNAKPAATIIWFRDglpQSEAATATEVLMDGKRKTTISQLLITPTDLDIGR 135
Cdd:cd05885     1 LVAPENPVVEVREQAV--EGGEVELSCLVPRSRPAATLRWYRD---RKELKGVSSGQENGKVWSVASTVRFRVDRKDDGG 75

                          90
                  ....*....|....*.
gi 1487364445 136 VYVCRCSNEAIPAGKE 151
Cdd:cd05885    76 IVICEAQNQALPSGHS 91

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 162 PTVTLSIQPQTVQEGERVTFTCLANANPEIKgYRWAKGGT-IIEDAKESKYETQVDYTFFTEPV--------SCEVRNDV 232
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPE-VSWFKDGQpLRSSDRFKVTYEGGTYTLTISNVqpddsgkyTCVATNSA 79

                          90
                  ....*....|.
gi 1487364445 233 GSTNVSILVDV 243
Cdd:pfam07679  80 GEAEASAELTV 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1487364445 249 IVMDPKPLITDIGSDVTLTCVWTGNPPLTLTWAK-------KESNMILGNSNQLHLKSVTQSDAGLYVCKA 312
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVA 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445  340 QYAVRGDRGKVECFIGSTPLPdRIAWgWKEKTLETGTLERYTVERSNTEdgvlSTLTINNVMEVDFQTrYNCTAWNAFGP 419
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPP-EVTW-YKQGGKLLAESGRFSVSRSGST----STLTISNVTPEDSGT-YTCAATNSSGS 76

                   ....*...
gi 1487364445  420 RTAIIQLE 427
Cdd:smart00410  77 ASSGTTLT 84

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1487364445  79 NLTCRAQNaKPAATIIWFRDGLPQSEaatatEVLMDGKRKTTISQLLITPTDLDIGRVYVCRCSNEA 145
Cdd:cd00096     2 TLTCSASG-NPPPTITWYKNGKPLPP-----SSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445  169 QPQTVQEGERVTFTCLANANPEIKGY-RWAKGGTIIEDAKESKYETQVDYTFFTEPVS--------CEVRNDVGSTNVSI 239
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTwYKQGGKLLAESGRFSVSRSGSTSTLTISNVTpedsgtytCAATNSSGSASSGT 81

                   ....
gi 1487364445  240 LVDV 243
Cdd:smart00410  82 TLTV 85

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1487364445  80 LTCRAQNAkPAATIIWFRDGLPQSEAATATEVLMDGKRKTTISQllitpTDLDIGrVYVCRCSNEAIPAgKEASIKLNV 158
Cdd:cd20970    22 FMCRAEGS-PEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNI-----RRSDMG-IYLCIASNGVPGS-VEKRITLQV 92

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 248 RIVMDPkplitdIGSDVTLTCVWTGNPPLTLTWAKKESNMILGNSNQ-------LHLKSVTQSDAGLYVC 310
Cdd:cd05856    12 RVIARP------VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGEnkkkkwtLSLKNLKPEDSGKYTC 75

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 331 PPIIS-SDSIQYAVRGDRGKVECFIGSTPLPdRIAWgwkektLETGTLERYTVERSNTEDGVLSTLTINNVMEVDFQTrY 409
Cdd:pfam13927   1 KPVITvSPSSVTVREGETVTLTCEATGSPPP-TITW------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGT-Y 72

                  ....*.
gi 1487364445 410 NCTAWN 415
Cdd:pfam13927  73 TCVASN 78

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1487364445   12 RITGVTDSGQFNLEITDAELSDDALYECQAT-EAALRSRRAKLNV 55
Cdd:smart00410  41 RFSVSRSGSTSTLTISNVTPEDSGTYTCAATnSSGSASSGTTLTV 85

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 1487364445 253 PKPLITDIGSDVTLTCVWTGNPPLTLTWA------KKESNMILGNSNQLHLKSVTQSDAGLYVCKAiVPRIGVGEREVAL 326
Cdd:cd20978     8 EKNVVVKGGQDVTLPCQVTGVPQPKITWLhngkplQGPMERATVEDGTLTIINVQPEDTGYYGCVA-TNEIGDIYTETLL 86

                  ..
gi 1487364445 327 LV 328
Cdd:cd20978    87 HV 88

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 1487364445 247 PRIVMDPKPLITDIGSDVTLTCVWTGNPPLTLTW--AKKESN-------------MILGNSNQLhLKSVTQSDAGLYVCK 311
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkhSKGSGVpqfqhivplngriQLLSNGSLL-IKHVLEEDSGYYLCK 80

                  .
gi 1487364445 312 A 312
Cdd:cd05734    81 V 81

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1487364445 166 LSIQPQ--TVQEGERVTFTCLANANPEIKGYRWAKGGTIIEDAKES------------KYETQVDYTFFTEPVSCEV 228
Cdd:cd05752     3 VSLDPPwtTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTSSSyrivaatvndsgEYRCQTQGSSLSDPVHLEV 79

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1487364445 333 IISSDSIQYAVRGDRGKVECFI-GSTPLPDRiawgW-KEKTLET-GTLERYTVERSNTEDGVLSTLTINNVMEVDfQTRY 409
Cdd:cd05735     6 ITSYPNTTLATKGQKKEMSCTAhGEKPIIVR----WeKEDTIINpSEMSRYLVTTKEVGDEVISTLQILPTVRED-SGFF 80

                          90       100
                  ....*....|....*....|.
gi 1487364445 410 NCTAWNAFGPRTAIIQLEEKE 430
Cdd:cd05735    81 SCHAINSYGEDRGIIQLTVQE 101