Second 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 second 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 (Neph1), Kirrel2 (Neph3), and Drosophila RST (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 70608146 154 ETRIDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTISQLLIEPTDLDIGRVFTCR 233
Cdd:cd05759   1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                        90
                ....*....|....*...
gi 70608146 234 SMNEAIPNGKETSIELDV 251
Cdd:cd05759  81 ARNEAIPNGKETSITLDV 98

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 70608146    54 RFSQEPADQTVVAGQRAVLPCvllNYSG----IVQWTKDGlalgmgQGLKAWPRYRVvgSADAGQYNLEITDAELSDDAS 129
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTC---TVTGtpdpEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                          90       100
                  ....*....|....*....|
gi 70608146   130 YECQAT-EAALRSRRAKLTV 148
Cdd:pfam07679  71 YTCVATnSAGEAEASAELTV 90

Second 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 second 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 (Neph1), Kirrel2 (Neph3), and Drosophila RST (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 70608146 154 ETRIDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTISQLLIEPTDLDIGRVFTCR 233
Cdd:cd05759   1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                        90
                ....*....|....*...
gi 70608146 234 SMNEAIPNGKETSIELDV 251
Cdd:cd05759  81 ARNEAIPNGKETSITLDV 98

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 70608146 357 VTLTCVWVGNPPLTLTWTKKDS---------NMVLSNSNQLLLKSVTQADAGTYTCRAIVPRIGVAEREV 417
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKplppssrdsRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146    54 RFSQEPADQTVVAGQRAVLPCvllNYSG----IVQWTKDGlalgmgQGLKAWPRYRVvgSADAGQYNLEITDAELSDDAS 129
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTC---TVTGtpdpEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                          90       100
                  ....*....|....*....|
gi 70608146   130 YECQAT-EAALRSRRAKLTV 148
Cdd:pfam07679  71 YTCVATnSAGEAEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146     59 PADQTVVAGQRAVLPCVLLNYSGI-VQWTKDGLALGMGQGlkawpryRVVGSADAGQYNLEITDAELSDDASYECQAT-E 136
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPeVTWYKQGGKLLAESG-------RFSVSRSGSTSTLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 70608146    137 AALRSRRAKLTV 148
Cdd:smart00410  74 SGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 70608146   254 PPTVTLSIEPQTVLEGERVIFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT 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 70608146    262 EPQTVLEGERVIFTCQATANPEIlGYRWAKGG--FLIEDAHESRYETNVDYSFFTEPVS--------CEVYNKVGSTNVS 331
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGgkLLAESGRFSVSRSGSTSTLTISNVTpedsgtytCAATNSSGSASSG 80

                   ....*
gi 70608146    332 TLVNV 336
Cdd:smart00410  81 TTLTV 85

Second 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 second 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 (Neph1), Kirrel2 (Neph3), and Drosophila RST (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 70608146 154 ETRIDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTISQLLIEPTDLDIGRVFTCR 233
Cdd:cd05759   1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                        90
                ....*....|....*...
gi 70608146 234 SMNEAIPNGKETSIELDV 251
Cdd:cd05759  81 ARNEAIPNGKETSITLDV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 70608146   340 PRIVVYPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKD---------SNMVLSNSNQLLLKSVTQADAGTYTCRA 405
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 70608146 357 VTLTCVWVGNPPLTLTWTKKDS---------NMVLSNSNQLLLKSVTQADAGTYTCRAIVPRIGVAEREV 417
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKplppssrdsRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 70608146   340 PRIVVYPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDS------NMVLSNSNQ---LLLKSVTQADAGTYTCRA 405
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdRFKVTYEGGtytLTISNVQPDDSGKYTCVA 75

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146   157 IDGGPVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTELLKDGKRETTISQLLIEPTDLDIGRVFTCRSMN 236
Cdd:pfam08205   3 IEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSY 82

                  ..
gi 70608146   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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 70608146 340 PRI-VVYPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNM----VLSNSNQLL-LKSVTQADAGTYTCRA 405
Cdd:cd04968   1 PSIkVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPssqwEITTSEPVLeIPNVQFEDEGTYECEA 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 70608146 149 LIPPE-------ETRIDGGPVillqagtpyNLTCRAFNAKPAATIIWFRDGTQQEGAVTSTEllkDGKRETTISQLLIEP 221
Cdd:cd05885   1 LVAPEnpvvevrEQAVEGGEV---------ELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRV 68

                        90       100       110
                ....*....|....*....|....*....|..
gi 70608146 222 TDLDIGRVFTCRSMNEAIPNG--KETSIELDV 251
Cdd:cd05885  69 DRKDDGGIVICEAQNQALPSGhsKQTQYVLDV 100

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 70608146 346 PKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMVLS-----NSNQLLLKSVTQADAGTYTCRA 405
Cdd:cd05725   4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA 68

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 70608146  57 QEPADQTVVAGQRAVLPCvllnyS---GI----VQWTKDGLALGMGQglkawPRYRVVGSAdagqyNLEITDAELSDDAS 129
Cdd:cd05724   2 VEPSDTQVAVGEMAVLEC-----SpprGHpeptVSWRKDGQPLNLDN-----ERVRIVDDG-----NLLIAEARKSDEGT 66

                        90       100
                ....*....|....*....|.
gi 70608146 130 YECQAT--EAALRSRRAKLTV 148
Cdd:cd05724  67 YKCVATnmVGERESRAARLSV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 70608146   254 PPTVTLSIEPQTVLEGERVIFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT 314
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLT 60

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 70608146   161 PVILLQAGTPYNLTCRAFNAKPAATIIWFRDGTQqegaVTSTELLKDGKRETTISQLLIEPTDLDIGRVFTCRSMNEAIP 240
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGT----LIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79

                  ....*..
gi 70608146   241 NGKETSI 247
Cdd:pfam00047  80 ATLSTSL 86

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 70608146  55 FSQEPADQTVVAGQRAVLPCVLlnySG----IVQWTKDG-LALGMGQGLKAWPRyrvvGSadagqynLEITDAELSDDAS 129
Cdd:cd20952   2 ILQGPQNQTVAVGGTVVLNCQA---TGepvpTISWLKDGvPLLGKDERITTLEN----GS-------LQIKGAEKSDTGE 67

                ....*.
gi 70608146 130 YECQAT 135
Cdd:cd20952  68 YTCVAL 73

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 70608146 353 IGSDVTLTCVWVGNPPLTLTWTKKDSNMVLSNSNQ-------LLLKSVTQADAGTYTCR 404
Cdd:cd05856  18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGEnkkkkwtLSLKNLKPEDSGKYTCH 76

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 70608146 340 PRIVVYPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNM---------VLSNSNQLLLKSVTQADAGTYTCRA 405
Cdd:cd05736   1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDInpklskqltLIANGSELHISNVRYEDTGAYTCIA 75

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 70608146 346 PKPTTTDIGSDVTLTCVWVGNPPLTLTWTKK----DSNMVLSN--SNQLLLKSVTQADAGTYTCRAiVPRIGVAEREVPL 419
Cdd:cd20978   8 EKNVVVKGGQDVTLPCQVTGVPQPKITWLHNgkplQGPMERATveDGTLTIINVQPEDTGYYGCVA-TNEIGDIYTETLL 86

                ..
gi 70608146 420 YV 421
Cdd:cd20978  87 HV 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146   346 PKPTTTDIGSDVTLTCV---WVGNPPLTLTWTKKDS--------------------------NMVLSNSN-QLLLKSVTQ 395
Cdd:pfam07686   3 PREVTVALGGSVTLPCTyssSMSEASTSVYWYRQPPgkgptfliayysngseegvkkgrfsgRGDPSNGDgSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*.
gi 70608146   396 ADAGTYTCRAIVPRIGVAEREVPLYV 421
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGKGTRLTV 108

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'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146 148 VLIPPEETRIDGGPVillqagtpyNLTCRAFNAKPA-ATIIWFRDGT-QQEGAVTSTELLKDGKRETTISQLLIEPTDLD 225
Cdd:cd00098   3 TLLPPSPEEKGGGKV---------TLVCLVSGFYPKdITVTWLKNGVpLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWD 73

                ....*...
gi 70608146 226 IGRVFTCR 233
Cdd:cd00098  74 EGATYTCV 81

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146 340 PRIVVYPKPTTTDIGSDVTLTCVWVGNPPLTLTW--------TKKDS----NMVLSNSNQLLLKSV----TQADAGTYTC 403
Cdd:cd07693   1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWlkngqpleTDKDDprshRIVLPSGSLFFLRVVhgrkGRSDEGVYVC 80

                ..
gi 70608146 404 RA 405
Cdd:cd07693  81 VA 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146    262 EPQTVLEGERVIFTCQATANPEIlGYRWAKGG--FLIEDAHESRYETNVDYSFFTEPVS--------CEVYNKVGSTNVS 331
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGgkLLAESGRFSVSRSGSTSTLTISNVTpedsgtytCAATNSSGSASSG 80

                   ....*
gi 70608146    332 TLVNV 336
Cdd:smart00410  81 TTLTV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 70608146 345 YPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNmvLSNSNQLLLKSVTQADAGTYTCRA 405
Cdd:cd20948   1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTF--QTSSQELFLPAITENNEGTYTCSA 59

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146    57 QEPADQTVVAGQRAVLPCVLLNYSGI----VQWTKDGLALGMGQGLKAW----------PRYRVVGSADAGQYNLEITDA 122
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEastsVYWYRQPPGKGPTFLIAYYsngseegvkkGRFSGRGDPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 70608146   123 ELSDDASYECQATEAALR--SRRAKLTVL 149
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGvfGKGTRLTVL 109

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 70608146 340 PRIVVYPKPTTTDI--GSDVTLTCVWVGNPPLTLTWTKK-------DSNMVLSNSNQLL-LKSVTQADAGTYTCRAIVPR 409
Cdd:cd20970   1 PVISTPQPSFTVTAreGENATFMCRAEGSPEPEISWTRNgnliiefNTRYIVRENGTTLtIRNIRRSDMGIYLCIASNGV 80

                        90
                ....*....|..
gi 70608146 410 IGVAEREVPLYV 421
Cdd:cd20970  81 PGSVEKRITLQV 92

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 70608146 354 GSDVTLTCVWVGNPPLTLTWTKKDSNMVLSN------SNQLLLKSVTQADAGTYTCRA 405
Cdd:cd04969  17 GGDVIIECKPKASPKPTISWSKGTELLTNSSricilpDGSLKIKNVTKSDEGKYTCFA 74

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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 has 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70608146  60 ADQTVVAGQRAVLPC-VLLNYSGIVQWT---KDGLALGMGQGLKAwPRYRVVGSAdAGQYNLEITDAELSDDASYECQAT 135
Cdd:cd05882   5 QDETVAVGGTVTLKCgVKEHDNSSLQWSntaQQTLYFGEKRALRD-NRIQLVKST-PTELIISISNVQLSDEGEYTCSIF 82

                        90
                ....*....|...
gi 70608146 136 EAALRSRRAKLTV 148
Cdd:cd05882  83 TMPVRTAKATVTV 95