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 1121904621 456 GPPIISSEAVQYAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 535
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1121904621 536 NCTAWNSFGPGTAIIQLE 553
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMgprspgsPPEAALSAQVLSNSNQLLLKSVTQADAGTYTC 436
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI-------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1121904621 437 RA 438
Cdd:pfam13927  75 VA 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1121904621 271 PPTVTLSIEPQTVQEGERVVFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT-EPVS--------CEVHN 340
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLTiSNVTrsdagtytCVASN 78

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 1121904621 456 GPPIISSEAVQYAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 535
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1121904621 536 NCTAWNSFGPGTAIIQLE 553
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMgprspgsPPEAALSAQVLSNSNQLLLKSVTQADAGTYTC 436
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI-------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1121904621 437 RA 438
Cdd:pfam13927  75 VA 76

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621  71 RFSQEPADQTVVAGQRAVLPCvllNYSG----IVQWTKDGlalgmgQGLKAWPRYRVmgSADAGQYNLEITDAELSDDAS 146
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTC---TVTGtpdpEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                          90       100
                  ....*....|....*....|
gi 1121904621 147 YECQAT-EAALRSRRAKLTV 165
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 1121904621 174 IDGGPVLLLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTISQLLINPTDLDIGRVFTCRSMN 253
Cdd:pfam08205   3 IEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSY 82

                  ..
gi 1121904621 254 EA 255
Cdd:pfam08205  83 GA 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1121904621 271 PPTVTLSIEPQTVQEGERVVFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT-EPVS--------CEVHN 340
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLTiSNVTrsdagtytCVASN 78

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 1121904621  74 QEPADQTVVAGQRAVLPCvllnyS---GI----VQWTKDGLALGMGQglkawPRYRVMGSAdagqyNLEITDAELSDDAS 146
Cdd:cd05724     2 VEPSDTQVAVGEMAVLEC-----SpprGHpeptVSWRKDGQPLNLDN-----ERVRIVDDG-----NLLIAEARKSDEGT 66

                          90       100
                  ....*....|....*....|.
gi 1121904621 147 YECQAT--EAALRSRRAKLTV 165
Cdd:cd05724    67 YKCVATnmVGERESRAARLSV 87

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 281 QTVQEGERVVFTCQATANPEILGYRWAKGGFLI--EDAHESRYETNVDYS---FFTEPVS------CEVHNKVGSTNVST 349
Cdd:cd05750     9 QTVQEGSKLVLKCEATSENPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSelqINKAKLEdsgeytCVVENILGKDTVTG 88

                  ....
gi 1121904621 350 LVNV 353
Cdd:cd05750    89 NVTV 92

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 1121904621 456 GPPIISSEAVQYAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 535
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 1121904621 536 NCTAWNSFGPGTAIIQLE 553
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 1121904621 456 GPPIISSEAVQYAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTHY 535
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1121904621 536 NCTAWNSFGPGTAIIQLE 553
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 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 1121904621 374 VTLTCVWVGNPPLTLTWTKKDSNMgprspgsPPEAALSAQVLSNSNQLLLKSVTQADAGTYTCRAIVPRIGVAERDV 450
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPL-------PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 358 RIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSnmgprspgsppeaalsaqVLSNSNQLLLKSVTQADAGTYTCR 437
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGS------------------AISSSPNFFTLSVSAEDSGTYTCV 62

                          90
                  ....*....|....*..
gi 1121904621 438 AIVPRIGVAERDVPLYV 454
Cdd:pfam13895  63 ARNGRGGKVSNPVELTV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621  363 PKPTTTDIGSDVTLTC-VWvGNPPLTLTWTKKdsnmGPRSPGSPPEAALSAQvlSNSNQLLLKSVTQADAGTYTCRAiVP 441
Cdd:smart00410   1 PPSVTVKEGESVTLSCeAS-GSPPPEVTWYKQ----GGKLLAESGRFSVSRS--GSTSTLTISNVTPEDSGTYTCAA-TN 72

                           90
                   ....*....|...
gi 1121904621  442 RIGVAERDVPLYV 454
Cdd:smart00410  73 SSGSASSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621   76 PADQTVVAGQRAVLPCVLLNYSGI-VQWTKDGLALGMGQGlkawpryRVMGSADAGQYNLEITDAELSDDASYECQAT-E 153
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPeVTWYKQGGKLLAESG-------RFSVSRSGSTSTLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 1121904621  154 AALRSRRAKLTV 165
Cdd:smart00410  74 SGSASSGTTLTV 85

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 1121904621 357 PRI-VVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDsnmgprspGSPPeaalSAQVLSNSNQLL-LKSVTQADAGTY 434
Cdd:cd04968     1 PSIkVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVD--------GSPS----SQWEITTSEPVLeIPNVQFEDEGTY 68

                  ....
gi 1121904621 435 TCRA 438
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 1121904621 166 LIPPE-------DTKIDGGPVlllqagtphNLTCRAFNAKPAATIIWFRDGTQQEGAVASTEllkDGKRETTISQLLINP 238
Cdd:cd05885     1 LVAPEnpvvevrEQAVEGGEV---------ELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRV 68

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1121904621 239 TDLDIGRVFTCRSMNEAIPNG--KETSIELDV 268
Cdd:cd05885    69 DRKDDGGIVICEAQNQALPSGhsKQTQYVLDV 100

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1121904621 271 PPTVTLSIEPQTVQEGERVVFTCQATANPEILgYRWAKGGFLIEDAHESRYETNVDYSFFT-EPVS--------CEVHN 340
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLTiSNVTrsdagtytCVASN 78

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1121904621 363 PKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMgPRSpgsppeaalSAQVLSNsNQLLLKSVTQADAGTYTCRA 438
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKG---------RYEILDD-HSLKIRKVTAGDMGSYTCVA 68

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 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWtkKDSNmGPRSPGSPPEAALSA--QVLSNSNqLLLKSVTQADAGTY 434
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVW--KHSK-GSGVPQFQHIVPLNGriQLLSNGS-LLIKHVLEEDSGYY 77

                  ....
gi 1121904621 435 TCRA 438
Cdd:cd05734    78 LCKV 81

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1121904621 370 IGSDVTLTCVWVGNPPLTLTWTKKDSNMGPRSPGSPPEAALSaqvlsnsnqLLLKSVTQADAGTYTCR 437
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWT---------LSLKNLKPEDSGKYTCH 76

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 1121904621  74 QEPADQTVVAGQRAVLPCvllnyS---GI----VQWTKDGLALGMGQglkawPRYRVMGSAdagqyNLEITDAELSDDAS 146
Cdd:cd05724     2 VEPSDTQVAVGEMAVLEC-----SpprGHpeptVSWRKDGQPLNLDN-----ERVRIVDDG-----NLLIAEARKSDEGT 66

                          90       100
                  ....*....|....*....|.
gi 1121904621 147 YECQAT--EAALRSRRAKLTV 165
Cdd:cd05724    67 YKCVATnmVGERESRAARLSV 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1121904621 361 VDPKPTTTDIGSDVTLTC-VWVGNPPLTLTWTKKDSNMgPRSPGSPPeaalsAQVLSNSNQLLLKSVTQADAGTYTCRA 438
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTL-IESLKVKH-----DNGRTTQSSLLISNVTKEDAGTYTCVV 73

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 1121904621 165 VLIPPEDTKIDGGPVlllqagtphNLTCRAFNAKPA-ATIIWFRDGTQQEGAVA-STELLKDGKRETTISQLLINPTDLD 242
Cdd:cd00098     3 TLLPPSPEEKGGGKV---------TLVCLVSGFYPKdITVTWLKNGVPLTSGVStSSPVEPNDGTYSVTSSLTVPPSDWD 73

                  ....*...
gi 1121904621 243 IGRVFTCR 250
Cdd:cd00098    74 EGATYTCV 81

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMGPRSPGsppeaalSAQVLSNSNQLLLKSVTQADAGTYTC 436
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSK-------QLTLIANGSELHISNVRYEDTGAYTC 73

                  ..
gi 1121904621 437 RA 438
Cdd:cd05736    74 IA 75

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); 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-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). 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. 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. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 165 VLIPPEDTKIDG--GPVLllqAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTISQLLINPTDLD 242
Cdd:cd05884     1 VLGVPEKPQISGftSPVM---EGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSSLDFHVDRDD 77

                          90
                  ....*....|....
gi 1121904621 243 IGRVFTCRSMNEAI 256
Cdd:cd05884    78 DGVAITCRVDHESL 91

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMgprsPGSpPEAALSAQVLSNSNqlllksVTQADAGTYTC 436
Cdd:cd05851     2 ADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM----PAT-AEISMSGAVLKIFN------IQPEDEGTYEC 70

                  ..
gi 1121904621 437 RA 438
Cdd:cd05851    71 EA 72

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 1121904621 357 PRIVVDPKPTTTDI--GSDVTLTCVWVGNPPLTLTWTKKDsnmgprspGSPPEAALSAQVLSNSNQLLLKSVTQADAGTY 434
Cdd:cd20970     1 PVISTPQPSFTVTAreGENATFMCRAEGSPEPEISWTRNG--------NLIIEFNTRYIVRENGTTLTIRNIRRSDMGIY 72

                  ....
gi 1121904621 435 TCRA 438
Cdd:cd20970    73 LCIA 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1121904621 361 VDPKPTTTDIGSDVTLTCVWVGNPPLTLTWtKKDSNMGPRSpgsppeaalSAQVLSNSNQLLLKSVTQADAGTYTC 436
Cdd:cd20957     6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLW-MKDGKPLGHS---------SRVQILSEDVLVIPSVKREDKGMYQC 71

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).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 358 RIVVDPKPTTTdIGSDVTLTCVWVGNPPLTLT---WTKKDSN-----------MGPRSPGSPPE--AALSAQVLSNSNQL 421
Cdd:cd05718     2 RVQVPTEVTGF-LGGSVTLPCSLTSPGTTKITqvtWMKIGAGssqnvavfhpqYGPSVPNPYAErvEFLAARLGLRNATL 80

                          90
                  ....*....|....*
gi 1121904621 422 LLKSVTQADAGTYTC 436
Cdd:cd05718    81 RIRNLRVEDEGNYIC 95

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1121904621 505 RYTVERTNSGSGVLSTLTINNVMEADfQTHYNCTAWNSFGPGTAIIQLEERE 556
Cdd:cd05735    51 RYLVTTKEVGDEVISTLQILPTVRED-SGFFSCHAINSYGEDRGIIQLTVQE 101

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121904621 357 PRIVVDPKPTTTDIGSDVTLTCVWVGNPPLTLTWTKKDSNMgprspgSPPEAALSAQVLSNSN----QLLLKSVTQADAG 432
Cdd:cd05869     3 PKITYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNI------SSEEKTLDGHIVVRSHarvsSLTLKYIQYTDAG 76